Rab proteins, a family of Ras-related small GTP-binding proteins, play a key role in regulating intracellular vesicle trafficking. Rab GDP dissociation inhibitor (Rab GDI or GDI3) forms a soluble complex with Rab proteins and thereby prevents the exchange of GDP for GTP. In mammals, there exist two major isoforms, Rab GDI (alpha) (also known as XAP-4) and Rab GDI (beta). While the mammalian Rab GDI (beta)-genes are ubiquitously expressed, the Rab GDI (alpha) genes are predominantly brain-specific. Since it is expressed predominantly in neural and sensory tissues, Rab GDI (alpha) may serve a specific function in neural signalmtransmission. The gene sequences for the Rab GDI proteins are extremely conserved in evolution, with substantial homology preserved across three eukaryotic kingdoms.