X-linked retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1)

RPGRIP1 is a multi-domain protein (coiled-coil domain, two C2 domains, C-terminal RPGR-interacting domain) predominantly localized to the ciliary transition zone of photoreceptors. It functions as a scaffold, anchoring RPGR and nephrocystin-4/NPHP4 at the connecting cilia. Defects in RPGRIP1 disrupt ciliary structure, impede protein trafficking between photoreceptor inner and outer segments, and lead to early-onset retinal dystrophies including Leber congenital amaurosis (LCA type 6) and cone-rod dystrophy (CORD13). While it is expressed in other ciliated cells, its indispensable function is in retinal photoreceptors. Gene therapy is in preclinical and early clinical stages for RPGRIP1-associated disease, with recent data showing that targeting residual central retina photoreceptors holds therapeutic promise. Mutations are rare but responsible for 5–6% of all LCA cases and characterized by premature vision loss while leaving the structure of central retina relatively intact for years. There are no approved drugs specifically targeting RPGRIP1, but genetic diagnosis and therapy development make it a bona fide therapeutic target in ophthalmology.

Other names

RPGRIP1RPGR-interacting protein 1RGI1LCA6CORD13RGRIPRPGRIPRPGRIP1dX-linked retinitis pigmentosa GTPase regulator-interacting protein 1

Gene augmentation therapy aiming to restore RPGRIP1 function in photoreceptors. No known small-molecule modulators.