The Retinitis Pigmentosa GTPase Regulator (RPGR) gene is significantly associated with retinal function [1,2,3]. Mutations in RPGR are the commonest cause of X-linked and recessive retinitis pigmentosa (RP), accounting for 10%-20% of all RP cases [1]. RPGR is located in photoreceptor connecting cilia, where it likely plays a role in the function of the ciliary gate, controlling access of both membrane and soluble proteins to the photoreceptor outer segment, though its exact function remains unknown [3].

In Rpgr knockout (KO) mice, photoreceptor degeneration occurs due to autophagy impairment in the retina [4]. The retinopathy phenotypes of Rpgr KO retinas can be rescued by adeno-associated virus-mediated transfer of pre-trans-splicing molecules, which produce normal Rpgr mRNAs via trans-splicing [4]. This shows that RPGR is essential for maintaining normal autophagy in the retina through accelerating GDP-to-GTP exchange of the small GTPase RAB37, thus contributing to retinal homeostasis [4].

In conclusion, RPGR is crucial for retinal function, especially in maintaining photoreceptor integrity through autophagy regulation. The Rpgr KO mouse model has been instrumental in revealing its role in autophagy-related retinal disease, providing insights into the mechanisms of RPGR-associated retinopathies and potential therapeutic strategies for treating such diseases [4].