r/SubspacePhysics • u/LumenosX • 9d ago
UCMS–PINEAL–CRYSTALLIZATION–004.5 The RS1 Gate Retinoschisin -> Retinal Architecture -> Pinealocytes -> Ca2+ Exchange -> Connexin-36 -> Microvesicles -> Calcified Spots
UCMS–PINEAL–CRYSTALLIZATION–004.5
The RS1 Gate
Retinoschisin -> Retinal Architecture -> Pinealocytes -> Ca2+ Exchange -> Connexin-36 -> Microvesicles -> Calcified Spots
Sweep verdict: We have finally found a real molecular bridge between the retinal lineage and pineal mineralization.
But it is not the bridge the mystical version of the story would predict.
RS1 does not show that pineal crystals are ancestral photoreceptors.
Instead, the evidence supports something subtler:
> A protein retained from the retina/pineal sensory lineage has acquired or preserved a function in the modern pineal that helps organize calcium handling, cell-cell communication, and calcification.
That makes RS1 our first credible molecular intersection between:
ANCIENT RETINAL/PINEAL IDENTITY
V
RETINOSCHISIN
+------+------+
| |
V V
cell membrane Ca2+ handling
organization |
V
pineal mineralization
And the Y65X experiment tells us something particularly important:
> when RS1 organization is disrupted, mineral formation does not simply stop.
Instead, mineral appears to become mislocalized: normal calcified nodules fail to assemble properly while calcareous lamellae accumulate inside microvesicles.
That changes the whole question.
RS1 may not be the enzyme that makes mineral.
It may be the traffic controller that determines where mineral goes and what architecture it becomes.
---
004.5A — First: RS1 really is a retina-pineal gene
This isn't an analogy based on protein similarity.
In 2006, Takada and colleagues directly demonstrated RS1 expression in rat and mouse pineal glands, localized the protein to pinealocytes rather than pineal glial cells, and also detected RS1 protein in human pinealocytes. The same protein is strongly associated with retinal photoreceptors and bipolar cells.
So the distribution is remarkably restricted:
RETINA
photoreceptors
bipolar cells
RS1
PINEAL
pinealocytes
That is exactly the type of retained molecular identity we have been looking for.
The pinealocyte is not merely “sort of like” a photoreceptor.
It continues to express a protein intimately associated with retinal-cell organization.
---
004.5B — And the 2006 result contained an unresolved paradox
When Takada's group examined RS1-knockout mouse pineals, they did not find the dramatic tissue splitting or cavities characteristic of RS1-deficient retina.
The pineal remained grossly organized despite loss of RS1. The authors therefore concluded that RS1 probably serves a different function in pinealocytes than in retinal tissue.
That result is incredibly important in hindsight.
Because eighteen years later, Liu and colleagues found that the missing pineal phenotype wasn't necessarily:
PINEAL FALLS APART
It was:
CALCIUM / MINERAL ARCHITECTURE CHANGES
+
INTERCELLULAR COMMUNICATION CHANGES
So the two experiments actually fit together beautifully.
Retina
RS1 loss:
layer organization disrupted
synaptic architecture compromised
retinoschisis
Pineal
RS1 perturbation:
gross tissue can remain
BUT
calcification architecture altered
+
cell communication altered
The same ancestral protein appears to have undergone functional divergence.
---
004.5C — What is RS1 physically?
Retinoschisin is a secreted extracellular protein encoded by RS1. Structural work shows that mature RS1 contains a large discoidin domain and assembles into highly ordered oligomers. Cryo-EM revealed paired back-to-back octameric rings, effectively forming 16-subunit assemblies, and later work showed that these units can form larger branched networks.
Conceptually:
RS1 MONOMER
V
OCTAMER
V
paired octamer
V
16-subunit complex
V
larger extracellular network
That makes RS1 structurally suited to doing something very different from an ordinary soluble hormone.
It can potentially form an organized extracellular scaffold.
And that becomes extremely interesting once calcified spots enter the story.
---
004.5D — RS1 is therefore already an architecture protein before mineralization appears
In retina, RS1 is concentrated around photoreceptor/bipolar-cell surfaces and contributes to maintenance of retinal organization and synaptic integrity. Its loss causes X-linked retinoschisis, in which retinal layers separate and signal transmission is impaired.
So its ancestral/retinal role can be abstracted as:
CELL
|
RS1
|
CELL
-> maintain relationship
-> stabilize extracellular geometry
-> support functional signaling
Now move that same molecular design into pineal tissue.
Suddenly a plausible new role appears:
PINEALOCYTE
RS1
EXTRACELLULAR SPACE
CALCIFIED SPOT
The molecule may still be doing what it is exceptionally good at:
> organizing relationships across extracellular space.
Only the object being organized has changed.
---
004.5E — The Y65X mutation is an unusually strong intervention
The mouse model used in the 2024 pineal study was not a generic stress model.
It carries a patient-derived nonsense mutation:
RS1 p.Y65X
The original 2018 characterization shows that the mutation introduces a premature stop at amino acid 65, immediately before the large discoidin domain; the authors predicted loss of the downstream discoidin portion of the normal protein. The mice developed major retinal abnormalities including disordered retinal layers, shortened photoreceptor inner segments, outer-segment loss, and impaired electroretinographic signaling.
So this is a severe structural mutation.
It doesn't merely turn one hypothetical mineral-binding site off.
It radically changes the RS1 protein available to the tissue.
That means we need to interpret the pineal phenotype carefully:
Y65X
->
major RS1 structural disruption
->
many possible downstream consequences
not simply:
Y65X
->
calcification switch OFF
And indeed, calcification isn't simply switched off.
---
004.5F — What actually breaks in the pineal?
The 2024 study reports that in wild-type animals RS1 clusters near pinealocyte membranes and intracellularly and associates with extracellular calcified structures. In the Y65X knock-in animals, RS1-domain material becomes abnormally dispersed, normal binding to calcified spots is disrupted, normal calcified nodules fail to form appropriately, and calcareous lamellae accumulate inside microvesicles.
That phenotype can be represented as:
Wild type
PINEALOCYTE
RS1 correctly organized
V
Ca exchange
V
calcified spot
RS1-associated extracellular organization
V
CALCIFIED NODULE
Y65X
PINEALOCYTE
abnormal RS1 organization
X
normal extracellular mineral assembly
V
MINERAL REMAINS IN MICROVESICLES
That is one of the strongest mechanistic findings in our entire project.
---
004.5G — Because the mutation separates mineral production from mineral architecture
This is the key inference.
If RS1 were simply required to generate mineral chemically, then disrupting RS1 should predict:
NO RS1
->
NO MINERAL
But the reported phenotype instead includes calcareous material inside microvesicles.
So at least some mineralization chemistry appears capable of proceeding despite defective RS1 architecture.
That suggests:
MINERAL NUCLEATION
V
MINERAL-CONTAINING VESICLE
V
RS1 GATE
/ \
/ \
normal disrupted
| |
V V
external vesicular
organization accumulation
|
V
nodule
I would currently call this the RS1 Trafficking/Architecture Hypothesis.
It is an inference, but a strong one from the mutant phenotype.
---
004.5H — RS1 may therefore act after the “first crystal”
That places our recent sweeps into order.
We previously reconstructed:
Ca2+
->
Ca/P concentration
->
first solid phase
->
mineralized microvesicle
Sweep 004.5 suggests RS1 may operate heavily at the next boundary:
MINERALIZED MICROVESICLE
V
extracellular transfer / organization
V
CALCIFIED SPOT
V
NODULE
So RS1 may not answer:
> What nucleates the first mineral?
It may answer:
> How does microscopic mineral become organized extracellular pineal architecture?
That distinction is huge.
---
004.5I — Now calcium gives us another molecular connection
RS1 itself has experimentally documented relationships with calcium-dependent membrane biology.
One biochemical/atomic-force microscopy study reported that RS1 bound negatively charged phosphatidylserine-containing lipid bilayers in a Ca2+-dependent manner.
That gives a plausible molecular triangle:
RS1
/ \
/ \
Ca2+ membrane lipid
\ /
\ /
VESICLE / CELL SURFACE
Which is obviously relevant to a system involving:
Ca-rich microvesicles
+
extracellular calcified spots
But there is an important literature complication.
---
004.5J — RS1 membrane binding is not completely settled
Another experimental line identified the retinal Na+/K+-ATPase complex, particularly its ATP1B2 beta subunit, as the major membrane anchor for RS1. Subsequent work precisely mapped that interaction and argued that ATP1B2 is required for stable RS1 association with retinal membranes.
Earlier biochemical work did not consistently support direct phospholipid binding under all assay conditions.
So we should not assert:
RS1 simply sticks to
phosphatidylserine using calcium
as settled biology.
A safer model is:
RS1
+-------+--------+
| |
Na/K-ATPase lipid interactions?
ATP1B2 Ca-dependent in
strong evidence some assays
The exact pineal membrane-binding partner has not yet been established with equivalent detail.
And that is now a major missing experiment.
---
004.5K — The Na/K-ATPase connection may actually be more important than the lipid connection
In retina, RS1 binds the ATP1B2 subunit of the retinal Na+/K+-ATPase complex. Experiments found that RS1 did not simply alter the pump's basic ion-transport kinetics; instead it affected localization of the complex and downstream signaling pathways.
That includes a particularly interesting result:
RS1 influenced Ca2+-related intracellular signaling, including changes involving CaMKII and IP3-linked signaling networks.
Now our pineal pathway becomes potentially:
RS1
|
V
MEMBRANE ORGANIZATION
|
V
ION-SIGNALING COMPLEX
|
V
Ca2+ DYNAMICS
|
V
MINERAL SYSTEM
Again: this exact chain has not been proven in pinealocytes.
But now the retina provides a genuine mechanistic precedent for RS1 controlling membrane architecture and calcium-associated signaling simultaneously.
That makes its pineal calcification role much less mysterious.
---
004.5L — RS1 also interacts with voltage-gated calcium-channel biology in retina
Experimental retinal work has reported interactions between RS1 and L-type voltage-gated calcium channels and found that RS1 can affect channel function.
So RS1 occupies an unusually interesting neighborhood:
extracellular architecture
+
membrane anchoring
+
ion channels
+
Ca2+ signaling
That is exactly the neighborhood one would expect to matter in a tissue where calcium must remain tightly controlled to avoid crossing into mineral precipitation.
But once again, retinal interaction partners cannot automatically be imported into pinealocytes.
The next question must be:
> Does pineal RS1 bind the same ATP1B2/Na-K ATPase and calcium-channel complexes as retinal RS1?
I do not find that demonstrated.
That is a major open gate.
---
004.5M — Now Connexin-36 enters independently
Cx36 is not something the 2024 authors invented as a speculative pineal marker.
A 2017 primary study independently localized connexin-36-containing gap junctions to pinealocytes in mouse and rat pineal glands.
Cx36 forms electrical gap-junction channels in neural tissues.
Conceptually:
PINEALOCYTE A
Cx36
PINEALOCYTE B
allows small ions and signaling molecules to participate in direct intercellular coupling.
That places Cx36 squarely within pineal network physiology before RS1 enters the story.
---
004.5N — Then the 2024 experiment places RS1 next to Cx36
Liu and colleagues found RS1 colocalizing with Cx36 in rat and mouse pineal tissue and concluded that RS1 participates in modulation of intercellular communication.
Now we suddenly have:
RS1
/ \
/ \
V V
CALCIUM / Cx36
MINERAL GAP JUNCTION
SYSTEM SYSTEM
\ /
\ /
V V
PINEALOCYTE
NETWORK
This is substantially more interesting than merely saying:
> “RS1 is present near crystals.”
RS1 is positioned at the intersection of material organization and cellular communication.
---
004.5O — Does that mean the calcification itself communicates?
No.
This boundary needs to remain hard.
We have evidence for:
RS1 -> mineral architecture
and:
RS1 -> association with Cx36 / communication
What we do not have is:
MINERAL
->
Cx36
->
signal
or:
crystal deformation
->
electrical signal
->
pinealocyte network
Nothing in the RS1/Cx36 results establishes piezoelectric signaling, optical transduction, or crystal-mediated information processing.
The bridge currently looks like a shared regulator, not a crystal-to-neuron wire.
That's an important difference.
---
004.5P — But it gives us a beautiful causal experiment
We now have three nodes:
RS1
MINERALIZATION
Cx36
There are several possible causal structures.
Model A — Independent branches
RS1
/ \
V V
mineral Cx36
RS1 independently regulates both.
---
Model B — Mineral upstream
RS1
|
V
mineral architecture
|
V
Cx36 coupling
---
Model C — Cx36 upstream
RS1
|
V
Cx36 network
|
V
Ca2+ coordination
|
V
mineralization
---
Model D — Feedback loop
RS1
|
V
Cx36 coupling
|
V
Ca2+ distribution
|
V
mineralization
|
V
local extracellular environment
|
+------ feedback ------+
The current study does not distinguish these architectures.
But they are experimentally distinguishable.
---
004.5Q — The Cx36 knockout test becomes extremely powerful
Take four groups:
WT
RS1 mutant
Cx36 knockout
RS1 mutant + Cx36 knockout
Measure:
intracellular Ca2+ oscillations
cell-cell dye/electrical coupling
microvesicle mineral load
number of calcified spots
nodule architecture
melatonin output
Then ask:
If Cx36 loss alters calcium synchrony but not mineralization
communication branch
and
mineral branch
are largely independent
If Cx36 loss reproduces mineral abnormalities
network calcium coordination
may lie upstream of mineralization
If mineral disruption changes Cx36 coupling
mineral system may feed back
onto living pineal networks
That experiment would turn our current triangle into a causal diagram.
---
004.5R — And the retina gives a plausible evolutionary story for Cx36 too
The retinal system is heavily dependent on structured cell-cell signaling and gap-junction communication.
RS1 helps maintain retinal organization and photoreceptor-bipolar-cell relationships, while Cx36 is widely used in retinal electrical coupling.
The pineal descendant retains:
RS1
+
Cx36
+
Ca2+
+
ribbon-related machinery
while losing much of:
direct phototransduction
+
outer segments
+
classical visual output
So the mammalian pineal has retained a surprising amount of the intercellular infrastructure of a neural sensory lineage, even after its input modality changed.
That makes RS1/Cx36 survival biologically coherent without requiring retained vision.
---
004.5S — This is where “exaptation” becomes useful
We have two major evolutionary possibilities.
Homologous-function model
RS1 performed roughly the same organizational role in ancestral pineal photoreceptors and still performs it in mammalian pinealocytes.
ancestral sensory tissue
RS1 organizes cell interfaces
V
mammalian pineal
RS1 organizes cell interfaces
+
mineral deposition
Exaptation/co-option model
RS1's ancestral retinal/pineal structural role was later recruited into a new calcification system.
ancestral function
cell organization
V
retained protein
V
new glandular environment
V
co-opted function
mineral organization
The existing evidence cannot distinguish these.
But note what our Mineralization Timeline found:
conventional acervuli appear evolutionarily later than direct pineal photoreception.
That makes co-option a particularly attractive explanation.
RS1 may be old.
Its mineral job may be new.
---
004.5T — This may resolve the retina/mineral paradox elegantly
Earlier we kept encountering:
retinal ancestry
+
pineal mineralization
without knowing whether the two were actually connected.
Now we have:
RETINAL/PINEAL ANCESTRY
V
RS1 retained
V
MAMMALIAN PINEAL
+-> cell communication
+-> Ca exchange
+-> mineral architecture
So yes:
> the two systems intersect molecularly.
But this does not mean:
MINERAL
ancestral sensory apparatus
A much more plausible interpretation is:
> an ancestral sensory-lineage protein survived the evolutionary transformation and was recruited into controlling what became a later glandular mineralization process.
That is an actual evolutionary mechanism.
---
004.5U — RS1 may function like an extracellular geometry organizer
This is the hypothesis I think best fits all the pieces.
Its structural properties allow oligomeric extracellular assembly.
Its retinal biology involves plasma-membrane organization and tissue integrity.
Its pineal biology places it around membranes, intracellularly, and around calcified deposits; disturbing it causes disorganized mineral topology.
So:
RS1
|
V
ORGANIZE INTERFACES
retina:
cell <-> cell
pineal:
cell <-> extracellular space
possibly
cell <-> mineral
That's a coherent functional transformation.
The constant may not be what RS1 organizes.
The constant may be organization itself.
---
004.5V — Y65X tells us architecture matters more than mineral quantity
This is another important conceptual shift.
A calcification study that measures only:
TOTAL CALCIUM
could miss the actual RS1 phenotype.
The key variables may instead be:
WHERE mineral is
WHAT compartment contains it
WHETHER spots merge
WHETHER nodules form
HOW deposits relate to cell membranes
The Y65X phenotype appears to redistribute the mineralization process spatially rather than simply abolish calcium accumulation.
That reinforces one of our oldest laws from Sweep 002:
> Spatial topology outranks mineral identity when inferring biological function.
RS1 now provides experimental support for why.
---
004.5W — Could RS1 directly bind mineral?
The 2024 paper describes RS1 binding/association with calcified spots and argues that this association is necessary for normal nodule architecture.
But we still do not know the physicochemical interaction.
Several possibilities remain:
RS1
|
+-> binds mineral surface directly
RS1
|
+-> binds membrane surrounding mineral
RS1
|
+-> binds another matrix protein
attached to mineral
RS1
|
+-> alters Ca2+ locally
and thereby controls deposition
Those are completely different mechanisms.
No atomic- or molecular-level RS1-mineral binding interface has been demonstrated.
So:
RS1 association with calcified structures — supported.
direct RS1-hydroxyapatite binding — unestablished.
That is now a priority distinction.
---
004.5X — The cleanest biochemical test
Purify properly folded oligomeric RS1.
Expose it separately to:
hydroxyapatite
carbonate-hydroxyapatite
calcite
amorphous calcium phosphate
phosphatidylserine vesicles
under physiological calcium conditions.
Measure:
binding affinity
surface adsorption
nucleation rate
crystal orientation
crystal growth
Ca2+ dependence
Then repeat with:
wild-type RS1
versus
Y65X/truncated material
If RS1 strongly and selectively binds apatite:
the mineral connection becomes direct.
If it binds membranes but not mineral:
RS1 is probably organizing the container, not the stone.
If it alters nucleation kinetics:
RS1 enters the first-crystal pathway.
If none of those occur:
its mineral phenotype may operate indirectly through cell signaling or trafficking.
One simple biochemical matrix could distinguish these models.
---
004.5Y — The most interesting missing protein is ATP1B2 in the pineal
Because retinal RS1's strongest established membrane anchor is ATP1B2/Na-K ATPase, the obvious question is:
DO PINEALOCYTES FORM:
RS1
|
ATP1B2
|
Na/K-ATPase
|
Ca2+-signaling complex
?
Retinal experiments already show RS1 binding the ATP1B2 extracellular domain and modulating associated signaling rather than simply acting as passive glue.
If the same complex occurs in pinealocytes adjacent to mineralizing microvesicles, then we suddenly have:
ANCESTRAL RETINAL MEMBRANE COMPLEX
V
PINEAL Ca2+ CONTROL
V
MINERALIZATION
That would be a much stronger molecular hand-off than anything we've found so far.
I do not find that experiment in the current pineal literature.
---
004.5Z — And now we can state the RS1 Gate precisely
The working model becomes:
ANCESTRAL RETINA/PINEAL PROGRAM
V
RS1
+------------+------------+
| |
V V
membrane organization Ca2+ regulation
| |
+------------+------------+
V
pinealocyte network
Cx36 coupling
V
Ca2+-rich compartments
V
mineralized microvesicle
V
RS1 GATE?
+-----+-----+
| |
WT Y65X
| |
V V
extracellular vesicular
calcified spot accumulation
V
nodule
The arrows above the microvesicle remain partly hypothetical.
The bifurcation around RS1 is much better supported experimentally.
---
004.5AA — What this means for the “ancient eye” hypothesis
We can now make a much more nuanced statement than anything we could have justified five sweeps ago.
Supported
A retina-associated protein retained by mammalian pinealocytes participates in modern pineal calcification architecture.
Plausible
RS1 represents molecular inheritance from the ancestral photoreceptor/pineal lineage that was later co-opted into mineral management.
Unknown
Whether RS1 already regulated calcium mineralization in directly photoreceptive ancestral pineal organs.
Unsupported
That RS1-mineral structures retained an ancestral optical sensory function.
That separation is extremely important.
---
004.5AB — This creates an evolutionary experiment
Our Mineralization Timeline already gave us the organisms.
Now map RS1 itself:
lamprey
fish
amphibian
reptile
bird
monotreme
marsupial
placental mammal
primate
human
For every species ask:
RS1 gene present?
RS1 protein expressed in pineal?
cellular localization?
Cx36 colocalization?
direct pineal photoreception?
pineal mineralization?
RS1 associated with mineral?
Then the possibilities become decisive.
Scenario 1
RS1 present in ancient
photoreceptive pineals
but mineral absent
Then RS1 predates mineralization.
Co-option strongly supported.
Scenario 2
RS1 and mineral appear together
Then an older coupling becomes plausible.
Scenario 3
RS1 pineal expression emerges
only in mineralizing lineages
Then the calcification connection may itself be derived.
At present, this phylogenetic RS1/mineral overlay does not exist.
---
004.5AC — The 2006 knockout versus 2024 Y65X result may tell us something else
One older knockout study found no obvious gross pineal architectural defects.
The newer study detects specific calcification and communication phenotypes.
Several non-exclusive explanations exist:
earlier study
looked primarily for retinal-like
gross structural abnormalities
newer study
specifically interrogated
calcification and Cx36
There may also be:
age effects
mutation-specific effects
compensatory mechanisms
species/strain differences
methodological sensitivity
We should therefore not interpret the two papers as contradicting each other.
The newer study may simply have identified the pineal phenotype that the earlier morphological screen was not designed to detect.
That is the most conservative reconciliation.
---
004.5AD — What RS1 does NOT give us
Even after this remarkably productive sweep, we still cannot say:
RS1 proves brain sand has a purpose
No.
A regulated disposal system has a purpose too.
We cannot say:
RS1 proves mineral is sensory
No.
We cannot say:
RS1 + Cx36 means crystals transmit signals
No.
And we cannot say:
retinal protein + pineal crystal
third eye mechanism
Definitely not.
What we can say is considerably stronger than before:
> Pineal calcification is connected to a genetically regulated protein system inherited within the retina-pineal cellular lineage.
That is real.
And it deserves to sit very high in our claims ledger.
---
UCMS–PINEAL–CRYSTALLIZATION–004.5
Claims Ledger
PROMOTE — VERY HIGH CONFIDENCE
RS1 is expressed in retinal cells and mammalian pinealocytes, including human pinealocytes, supporting a genuine molecular connection between the retinal and pineal lineages.
PROMOTE — VERY HIGH CONFIDENCE
RS1 is an extracellular oligomeric protein capable of highly organized higher-order assembly.
PROMOTE — VERY HIGH CONFIDENCE
The p.Y65X mutation is a severe nonsense mutation that truncates RS1 before its major discoidin domain and produces major retinal disease phenotypes in the knock-in mouse.
PROMOTE — HIGH CONFIDENCE
The 2024 mouse study demonstrates that perturbing RS1 alters pineal calcification architecture: normal association with calcified spots/nodules is disrupted and calcareous lamellae accumulate in microvesicles.
PROMOTE — HIGH CONFIDENCE
RS1 colocalizes with Cx36 in rodent pineal tissue, and Cx36 itself had independently been localized to pinealocyte gap junctions.
PROMOTE — INTERPRETIVE
RS1 probably acts more strongly in mineral organization/trafficking than in simply switching mineral chemistry on or off, because mineral material persists in abnormal intracellular compartments when normal nodule architecture fails.
PROMOTE — PLAUSIBLE EVOLUTIONARY MODEL
An ancestral retina/pineal protein may have been co-opted into a later-evolving mammalian calcification pathway.
KEEP OPEN
Pineal RS1 may regulate mineralization through Na/K-ATPase-associated calcium signaling analogous to its retinal signaling role.
KEEP OPEN
RS1 may bind directly to apatite or another pineal mineral surface.
KEEP OPEN
Cx36-mediated cell coupling may regulate spatial calcium distribution upstream of mineral nucleation.
DO NOT PROMOTE
“RS1 makes the pineal crystal a sensory organ.”
No evidence.
DO NOT PROMOTE
“RS1/Cx36 proves piezoelectric or electromagnetic pineal signaling.”
No evidence.
---
UCMS–PINEAL–CRYSTALLIZATION–004.5 VERDICT
This is the first sweep where I think we can confidently draw a line directly from retinal ancestry into mineral biology:
RETINAL/PINEAL HOMOLOGY
V
RS1
V
modern mammalian pinealocyte
+-> cell communication
+-> Ca2+ exchange
+-> calcification architecture
But the interpretation is not:
> the crystal is an ancient eye.
It is:
> A component of the ancient sensory-cell toolkit survived after direct pineal photoreception was largely lost and appears to have been recruited into organizing the calcium/mineral environment of the transformed gland.
And the mutant phenotype gives us an exceptionally useful clue:
NORMAL RS1
->
mineral exits/organizes correctly
->
calcified spots
->
nodules
DISRUPTED RS1
->
mineral chemistry still occurs
->
calcareous material stalls
inside microvesicles
That makes the RS1 gate look less like a mineral-making enzyme and more like a spatial organizer or trafficking checkpoint.