Ras-related protein in brain (Rab GTPase) (Rab)

Rab GTPases constitute the largest family of small monomeric G proteins, encompassing approximately 70 members in humans that act as master regulators of intracellular membrane trafficking [2, 6]. These enzymes function as molecular switches, cycling between an active GTP-bound state associated with specific organelle membranes and an inactive GDP-bound state in the cytosol, a process regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) [3, 10]. By recruiting diverse effector proteins, Rabs coordinate every stage of vesicle transport, including cargo selection, budding, cytoskeletal movement, tethering, and fusion [3, 4, 21]. In disease, Rab dysfunction is a major driver of cancer progression, where specific isoforms like Rab27 and Rab11 facilitate tumor invasion, migration, and the secretion of pro-tumorigenic exosomes [11, 18]. In neurodegenerative disorders such as Parkinson's and Alzheimer's diseases, altered Rab activity (e.g., Rab5, Rab7) leads to impaired protein degradation and autophagic failure [10, 15, 17]. While direct pharmacological targeting is challenging due to the high nucleotide affinity of the GTP-binding pocket, therapeutic strategies currently include inhibitors of post-translational prenylation, modulators of GEF/GAP interactions, and small molecules designed to disrupt Rab-effector protein-protein interactions [4, 16].

Other names

Rab proteinsRas-related proteins in brainRas-associated binding proteinsSmall GTP-binding proteinsRab family GTPases

Inhibition of guanine nucleotide exchange (GEF blockade), competitive inhibition of effector protein recruitment, or blocking of post-translational C-terminal prenylation required for membrane association [4, 8, 10].