{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRS1, the gene encoding retinoschisin, produces a 24‐kDa secreted protein characterized by a discoidin domain that is essential for retinal structural integrity. Retinoschisin is synthesized by photoreceptors and bipolar cells and rapidly assembles into a large, disulfide‐linked homo‐octamer. This precise multimerization—supported by critical disulfide bonds within and outside its discoidin domain—not only stabilizes its native conformation but also is indispensable for its function as a cell adhesion molecule that maintains retinal layer architecture and the synaptic organization between photoreceptors and bipolar cells. Mutations that disrupt proper folding, octamer assembly, or secretion lead to intracellular retention and loss of function, events that underpin the pathology seen in X‑linked retinoschisis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n\n"}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its adhesive role, retinoschisin interacts with specific cell-surface proteins to reinforce retinal cell organization and modulate signaling pathways. In particular, retinoschisin binds to the Na/K‑ATPase complex on photoreceptor and bipolar cell surfaces—an interaction crucial for anchoring the protein to membranes and for coordinating downstream cascades involving regulators such as Src and CaMK2. Structural modeling studies further reveal that distinct regions outside the central discoidin domain serve as interfaces for RS1 multimerization into higher‐order structures (such as branched networks), suggesting that these assemblies stabilize intercellular interactions in the retina. Co‐assembly properties emerging from wild‐type and mutant proteins also emphasize the delicate balance required for retinoschisin function, with disruptions leading to the characteristic splitting of the inner retinal layers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stephen K Sikkink, Susmito Biswas, Neil R A Parry, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "RS1, a discoidin domain-containing retinal cell adhesion protein associated with X-linked retinoschisis, exists as a novel disulfide-linked octamer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M413117200"}], "href": "https://doi.org/10.1074/jbc.M413117200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15644328"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15644328"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Tao Wang, Caroline T Waters, Alex M K Rothman, et al. 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