{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPeripherin‐2 (PRPH2), also known as peripherin/rds, is a photoreceptor‐specific tetraspanin glycoprotein that localizes predominantly to the outer segment membranes of both rods and cones. It plays an essential role in the formation and maintenance of the disk membranes that are critical for visual transduction, mediating key membrane fusion events and organizing high‐curvature regions of nascent disks. In its normal state, PRPH2 is required for proper outer segment morphogenesis and renewal, ensuring the intricate architecture that underlies photoreceptor function and survival."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAt the molecular level, PRPH2 molecules assemble into core tetramers and can further polymerize into higher‐order complexes that are critical for generating the highly curved disk rims. The precise oligomerization and complex formation, including interactions with its homolog ROM1, underpin its fusogenic activity and efficient incorporation into the outer segment. In addition, studies indicate that proper intracellular trafficking—entailing specialized signals such as those regulating late endosome sorting and controlled splicing—ensures that PRPH2 is accurately delivered to its destination in photoreceptors, a process that is essential for the establishment of the unique membrane domains."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPerturbations of these finely tuned processes—whether through mutations that affect oligomerization, alter splicing, or disturb the targeting signals—lead to a broad spectrum of retinal dystrophies. Genetic and biochemical studies, along with detailed genotype–phenotype correlations, have revealed that defective PRPH2 function accounts for diverse clinical presentations ranging from retinitis pigmentosa to various forms of macular and pattern dystrophies. The observed phenotypic heterogeneity underscores that even subtle alterations in PRPH2’s structure or expression can compromise the integrity of the outer segment, ultimately impairing photoreceptor viability and vision."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "46"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kathleen Boesze-Battaglia, Andrew F X Goldberg "}, {"type": "b", "children": [{"type": "t", "text": "Photoreceptor renewal: a role for peripherin/rds."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Rev Cytol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0074-7696(02)17015-x"}], "href": "https://doi.org/10.1016/s0074-7696(02"}, {"type": "t", "text": "17015-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12019563"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12019563"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Monika Damek-Poprawa, Jennifer Krouse, Cheryl Gretzula, et al. 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