PRPH2 encodes peripherin-2, a photoreceptor-specific tetraspanin protein essential for rod and cone outer segment formation and maintenance 1. The protein is critical for retinal outer segment disk morphogenesis and organization of photoreceptor inner segments, with roles in maintaining outer nuclear layer thickness 2. PRPH2 mutations cause diverse inherited retinal diseases, with over 90 disease-causing variants identified 1. These mutations are associated with multiple phenotypes including retinitis pigmentosa, pattern dystrophy, macular dystrophies, and central areolar choroidal dystrophy 342. In a large UK cohort, PRPH2 variants contributed to disease in a substantial proportion of inherited retinal disease families, associating with both dominant and recessive phenotypes 3. Mouse models carrying the p.Arg195Leu mutation demonstrate progressive retinal degeneration with reduced visual function, altered outer segment structure, and synaptic remodeling with microglial activation, recapitulating human disease 5. Pathogenic mechanisms involve haploinsufficiency and protein misfolding, complicating therapeutic development 1. Gene therapy approaches using adeno-associated viruses have shown promise in animal models but face challenges due to the critical requirement for precise peripherin-2 dosage 1.