GDI2 protein: research progress and its mechanisms in diseases

GDP dissociation inhibitor 2 (GDI2), also termed RabGDIβ, is an evolutionarily conserved Rab GDP dissociation inhibitor that is broadly expressed across species and is required for fundamental cellular functions. Mechanistically, GDI2 controls the cycling of Rab small GTPases between membranes and the cytosol, thereby regulating Rab-dependent membrane targeting, intracellular trafficking, and downstream signal transduction. Increasing evidence indicates that GDI2 is not only a constitutive component of the membrane-transport machinery; aberrant GDI2 expression or activity is associated with diverse human diseases. Notably, the functional consequences of GDI2 dysregulation appear to be context dependent, with reported involvement in cancer, neurodegeneration, immune dysregulation, and metabolic disease. Here, we synthesize current knowledge of GDI2 biology, highlighting recent advances that delineate its molecular features and its roles in maintaining membrane-trafficking homeostasis, remodeling signaling networks, and shaping disease-relevant cellular phenotypes. We also discuss the translational implications of GDI2 as a potential diagnostic biomarker and therapeutic target, and we propose a conceptual framework to guide mechanistic interpretation and the development of GDI2-directed therapeutic strategies.