Ras-related protein Rab-35 (RAB35)

Rab35 is a small GTPase belonging to the Ras oncogene family that acts as a master regulator of membrane trafficking, particularly in endocytic recycling, vesicle fusion, and cytokinesis[7][6][8]. It cycles between a GDP-bound inactive state and a GTP-bound active state to control the recruitment of downstream effectors responsible for vesicle formation and fusion. Rab35 is essential for fast membrane recycling from endosomes to the plasma membrane and regulates several crucial cellular functions such as the actin cytoskeleton, cell shape changes, cilium formation, and exocytosis of endothelial Weibel–Palade bodies[2][3][8]. Mutations in Rab35 are linked to cancer, developmental and neurological disorders, and ciliopathies, highlighting its role in human disease pathogenesis[4][7][3]. Although not currently a therapeutic drug target, Rab35's regulatory domains and gain-of-function mutations are under investigation for their oncogenic and cell cycle impact, particularly in the context of RAS-dependent signaling pathways[4][5].

Other names

RAB35Ras-related protein Rab-35RAB1CRAYH-rayGTP-binding protein RAYRas-related protein Rab-1CRas-related protein rab-1c (GTP-binding protein ray)

Molecules (mutations or biologics) can activate or inhibit Rab35 GTPase activity, affecting vesicle trafficking, cytoskeletal organization, and downstream signaling such as RAS/MAPK or PI3K/AKT activation. Rab35 mutations (A151T, F161L) possess gain-of-function properties analogous to RAS mutations, triggering constitutive signaling.