Rab28, a member of the RAS oncogene family, is a farnesylated, small GTPase. It is involved in multiple biological processes. In the retina, it plays a crucial role in outer segment phagocytosis (OSP) of cone photoreceptors and is associated with visual cycle function. It is also implicated in the regulation of extracellular vesicle shedding in cilia, GLUT4 trafficking in insulin target cells, and may participate in the NF-κB nuclear transport in endothelial cells [1-4, 7]. Zebrafish and mouse models have been valuable for studying Rab28 function [1,2,3,4].

In zebrafish, rab28-/-knockouts (KO) display defective outer segment shedding, with reduced shed outer segment material/phagosomes in the RPE at 1 month post-fertilization. Restoring wild-type zebrafish Rab28 specifically in cone photoreceptors rescues the OSP defects, suggesting potential for gene therapy in RAB28-associated cone-rod dystrophy (arCORD) [1,2,3]. In mice, Rab28-/-mice recapitulate features of human arCORD, including reduced cone and rod electroretinography responses, progressive retina degeneration, and almost absent cone phagosomes [4].

In conclusion, Rab28 is essential for normal function in the retina, particularly in cone-related processes such as OSP and visual cycle function. The gene knockout mouse models have been instrumental in revealing its role in arCORD, providing insights into the disease mechanism and potential therapeutic strategies for this inherited retinal degeneration [1,2,4].