RPGR (retinitis pigmentosa GTPase regulator) is an X-linked gene encoding a guanine-nucleotide exchange factor (GEF) that activates RAB8A and RAB37 small GTPases by promoting conversion of inactive RAB-GDP to active RAB-GTP 1. Through RAB8A activation, RPGR facilitates ciliary trafficking and intracellular localization within photoreceptor cilia 1. RPGR regulates cilia formation by modulating actin stress filaments and may coordinate microtubule organization and intraflagellar transport 2. These functions are critical for photoreceptor integrity and retinal homeostasis. RPGR mutations cause X-linked retinitis pigmentosa (XLRP) and cone-rod dystrophy, representing approximately 5% of inherited retinal disease cases in clinical cohorts 34. The gene demonstrates genetic heterogeneity, with diverse phenotypes arising from variants in the same gene, partly reflecting limitations in detecting mutations in the repetitive exon 15 region 45. Gene replacement therapy using AAV5-hRKp.RPGR demonstrated clinical efficacy and safety in phase 1/2 trials, with improvements in retinal sensitivity and functional vision, supporting its therapeutic potential 67. These findings establish RPGR dysfunction in progressive photoreceptor degeneration and validate gene therapy as a treatment approach for RPGR-associated retinopathies.