Retinitis pigmentosa GTPase regulator (RPGR) (RPGR)

Retinitis pigmentosa GTPase regulator (RPGR) is a critical protein localized to the connecting cilia of retinal photoreceptor cells, where it regulates the trafficking of proteins between the inner and outer segments (UniProt Q92834). The ORF15 isoform, which contains a highly repetitive and mutation-prone C-terminal domain, is the most biologically relevant form in the human retina (Vervoort et al., 2000, Nature Genetics). Mutations in the RPGR gene, particularly within the ORF15 region, are responsible for the majority of cases of X-linked retinitis pigmentosa (XLRP), a severe form of inherited retinal degeneration characterized by progressive loss of rod and cone photoreceptors (NIH GARD). As a therapeutic target, RPGR is currently being addressed through gene replacement therapies, such as botaretigene loguparvovec and laruparetigene zovaparvovec, which utilize adeno-associated virus (AAV) vectors to deliver a functional copy of the RPGR-ORF15 sequence to the subretinal space (ClinicalTrials.gov NCT03116113). These interventions aim to restore protein function, stabilize the ellipsoid zone, and prevent further vision loss in affected individuals.

Other names

ORF15X-linked retinitis pigmentosa GTPase regulatorRP3COD1CORDX1PCDX

Gene replacement therapy via adeno-associated virus (AAV) vector delivery of a functional RPGR-ORF15 cDNA to restore protein expression in photoreceptor cells (ClinicalTrials.gov NCT03116113).