Gene RPE65
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Also known as
Retinal Pigment Epithelium-Specific Protein 65kDa, LCA2, RP20, p63Overview
RPE65 (Retinal Pigment Epithelium-Specific Protein 65kDa) encodes an isomerohydrolase enzyme that plays an essential role in the visual cycle, the biochemical pathway that enables vision in the retina. This protein is specifically expressed in the retinal pigment epithelium (RPE), where it catalyzes the conversion of all-trans-retinyl ester to 11-cis-retinol, a critical step in regenerating the light-sensitive chromophore that enables photoreceptor cells to detect light. Without functional RPE65, the visual cycle cannot proceed efficiently, leading to progressive vision loss.Mutations in RPE65 cause Leber congenital amaurosis type 2 (LCA2) and early-onset severe retinal dystrophy, both of which result in severe vision impairment from infancy or early childhood. Affected individuals typically experience night blindness, decreased visual acuity, and progressive retinal degeneration. RPE65-associated retinal disease is historically significant as the first inherited retinal disorder successfully treated with gene therapy. The FDA-approved gene therapy voretigene neparvovec (Luxturna) delivers a functional copy of the RPE65 gene to retinal cells, demonstrating remarkable vision improvements in many treated patients and establishing a milestone in the treatment of genetic eye diseases.