GDP dissociation inhibitor 2 (GDI2)

GDP dissociation inhibitor 2 (GDI2) is a ubiquitously expressed cytosolic regulatory protein that controls the activity of Rab family small GTPases by preventing their GDP-GTP exchange and extracting Rab proteins from membranes, thereby regulating intracellular vesicular trafficking. GDI2 acts on a broad range of Rab proteins and is critical for endomembrane homeostasis. Recent research has identified GDI2 as a manipulable cancer target, particularly in pancreatic cancer, where its inhibition or selective degradation can induce a non-apoptotic form of cell death termed paraptosis, involving ER stress and cytoplasmic vacuolization. Experimental small molecules (e.g., BQZ-485 and derivatives) can inhibit or degrade GDI2, providing a novel therapeutic strategy for tumors with high GDI2 expression. GDI2 plays additional roles in ciliogenesis and may be involved in neurodevelopmental disorders and ciliopathies[1][2][3][4][5].

Other names

Rab GDP dissociation inhibitor betaRABGDIBRab GDI betaGDI-2Guanosine diphosphate dissociation inhibitor 2HEL-S-46eEpididymis secretory sperm binding protein Li 46e

Inhibition of GDI2-Rab1A interaction, disrupting vesicular transport and inducing paraptosis (by small molecule inhibitor BQZ-485 and derivatives) Chemical degradation via the ubiquitin–proteasome system (by experimental degrader 21)