GAPVD1 (GTPase activating protein and VPS9 domains 1) is a multifunctional regulator of small GTPases that controls endocytic trafficking and receptor internalization. As a guanine nucleotide exchange factor (GEF) for RAB31, GAPVD1 regulates GLUT4 trafficking by maintaining RAB31 in an active state, promoting glucose transporter cycling between intracellular storage vesicles and early endosomes 1. Upon insulin stimulation, GAPVD1 translocates to the plasma membrane, releasing GLUT4 for glucose uptake. GAPVD1 also regulates endocytosis through phosphorylation by casein kinase 1δ/ε; phosphorylation is essential for efficient transferrin and EGF internalization 2. Clinically, GAPVD1 mutations cause steroid-resistant nephrotic syndrome through impaired RAB5 regulation and reduced nephrin binding, disrupting podocyte endocytosis and cell migration 1. In cancer biology, GAPVD1 participates in triple-negative breast cancer stemness through VEGFA/NRP-1 signaling and Wnt/β-catenin pathway activation 3, while circular GAPVD1 suppresses gastric cancer progression via miR-4424/STK4 regulation 4. GAPVD1 expression levels correlate with interferon-β response in multiple sclerosis patients 5, suggesting pharmacogenetic significance.