RPGRIP1 encodes a scaffolding protein essential for photoreceptor ciliary function and survival. Primary function: RPGRIP1 localizes to the photoreceptor connecting cilium, where it anchors and enables correct positioning of the RPGR protein 1. This interaction is critical for maintaining the structural integrity of the ciliary axoneme 1. Mechanism: RPGRIP1 contains a C-terminal RPGR-interacting domain and coiled-coil domain 1, and is required for normal disk morphogenesis and outer segment organization in photoreceptors 1. Multiple RPGRIP1 isoforms exist with distinct subcellular localizations and functions, suggesting both ciliary and lysosome-related roles 2. Disease relevance: Recessive RPGRIP1 mutations cause Leber congenital amaurosis 6 (LCA6), accounting for 5-6% of LCA cases 3, and cone-rod dystrophy. RPGRIP1 is among the five most frequently mutated genes in LCA cohorts 4. Photoreceptors lacking functional RPGRIP1 cannot maintain light-sensing outer segments, causing early retinal function loss 3. Clinical significance: Patients typically retain central retinal photoreceptors into adulthood 3, enabling potential therapeutic intervention. Gene augmentation therapy in murine models effectively slows photoreceptor degeneration 5 and rescues disease phenotypes in human iPSC-derived retinal organoids 6, supporting future clinical trial development.