RP2

RP2, or retinitis pigmentosa 2, is a gene on the X chromosome that encodes the RP2 protein. Mutations in RP2 cause X-linked retinitis pigmentosa, a hereditary retinal dystrophy characterized by progressive degeneration of photoreceptors, leading to night blindness and gradual loss of peripheral vision.

Function and role: The RP2 protein is involved in intracellular trafficking within photoreceptor cells. It acts as a regulator of small GTPases and participates in the trafficking of ciliary cargo, including opsins, across the photoreceptor connecting cilium. This activity is important for maintaining photoreceptor structure and function.

Structure and localization: RP2 is found in the cytoplasm of retinal cells and associates with ciliary and basal body structures near the photoreceptor connecting cilium, consistent with a role in ciliary trafficking.

Genetics: Inheritance is X-linked recessive; most affected individuals are male, while carrier females may show variable, milder signs. Variants include missense, nonsense, splice-site, and frameshift mutations that typically disrupt RP2 function or localization.

Clinical features: Presentation usually occurs in adolescence or early adulthood, with nyctalopia (night blindness) and progressive constriction of the visual field. Fundus and imaging findings reflect retinal degeneration, and electrophysiological testing shows reduced rod and cone function. Genetic testing can confirm RP2 mutations.

Diagnosis and testing: Diagnosis combines clinical examination, imaging and functional tests, and targeted or panel-based genetic testing for inherited retinal diseases that includes RP2 variants.

Treatment and prognosis: There is no cure, and management is supportive, focusing on vision rehabilitation and monitoring. Research on gene therapy and other targeted approaches for RP2-related disease is ongoing, aiming to restore RP2 function or compensate for its loss.

History: RP2 was identified as a disease gene for X-linked retinitis pigmentosa in the early 21st century, contributing to understanding of ciliary mechanisms in retinal disease.