RPE65

RPE65 retinal pigment epithelial 65 kDa protein is a key enzyme belonging to the carotenoid cleavage dioxygenase superfamily, which plays a crucial role in the visual cycle of vertebrates. RPE65 is a membrane-bound protein with an N-terminal signal peptide and a C-terminal esterase domain. Its three-dimensional structure contains multiple transmembrane helices and extracellular loops. The main function of RPE65 is to catalyze the hydrolysis and isomerization of all-trans-retinyl esters in the visual cycle, producing 11-cis-retinol, which is a key step in the regeneration of visual pigments and ensures the continuous functioning of vision. The main signaling pathways involved in RPE65 include the visual cycle, photoreceptor signaling pathway, and photoprotection, in which it indirectly participates in the transmission of photoreceptor signaling by maintaining the regeneration of visual pigments, and plays a role in resisting light-induced retinal damage. Mutations in RPE65 are associated with diseases such as Leber congenital amaurosis LCA and retinitis pigmentosa RP. Gene therapy targeting RPE65 has become a cutting-edge method for treating these diseases, among which voretigene neparvovec-rzyl is the first FDA-approved drug for the treatment of LCA/RP caused by RPE65 gene mutations.