GDI2

GDP dissociation inhibitor 2 (GDI2) is a cytosolic protein encoded by the GDI2 gene in humans. Also known as Rab GDP dissociation inhibitor beta, it is a member of the GDI family that regulates Rab GTPases, key regulators of vesicular trafficking in eukaryotic cells.

GDI2 binds to Rab proteins in their GDP-bound state and shields their prenylated membrane-anchoring tails, preventing spontaneous activation or membrane reassociation. This allows Rabs to be extracted from membranes and stabilized in the cytosol, facilitating cycling between membrane-associated and cytosolic pools. By modulating the availability of Rab GTPases, GDI2 influences trafficking steps in endocytosis, recycling, and secretory pathways among organelles such as the endosomes, Golgi apparatus, and plasma membrane.

In human cells, GDI2 is expressed broadly and resides primarily in the cytosol, with regulated interactions that respond to the Rab GTPase cycle. It functions alongside other Rab regulators and can work with GDI1 in some contexts, reflecting redundancy within the GDI family.

Clinical and research notes: Disruptions in Rab cycling can impact cellular trafficking and have been examined in various diseases, but specific disease associations for GDI2 are not well established. Ongoing studies explore the role of GDI2 in vesicle trafficking, neuronal function, and cancer biology.