GDI1 (GDP dissociation inhibitor 1) is an X-linked gene encoding a regulatory protein that controls small GTPase activity, particularly Rab proteins involved in vesicle trafficking. GDI1 functions by inhibiting GDP dissociation from Rab proteins and promoting their extraction from membranes in the inactive GDP-bound state 1. This regulation is critical for intracellular transport processes including synaptic vesicle trafficking and axonal transport 2. GDI1 mutations cause X-linked intellectual developmental disorder 41, characterized by selective cognitive impairment affecting short-term temporal associations and memory formation 3. Gdi1-knockout mice display deficits in associative memory with altered social behavior, suggesting the gene's role in forebrain functions 3. Recent evidence reveals that GDI1 loss impairs working memory through dysregulated astrocyte glycolysis, providing a novel neuroglial mechanism for neurodevelopmental disease 4. Elevated GDI1 emerges as a biomarker for neurodegenerative disease: it is elevated in cerebrospinal fluid of frontotemporal dementia and Alzheimer's disease patients, differentiating amyloid-positive from amyloid-negative individuals 5. Paradoxically, GDI1 inhibition attenuates β-amyloid-induced neurotoxicity in Alzheimer's models 6. Additionally, RAB3A hyperphosphorylation in Parkinson's disease pathogenesis disrupts GDI1 binding, impairing synaptic vesicle precursor trafficking 7.