AGAP1 is an Arf GTPase-activating protein that functions as a central regulator of endolysosomal trafficking and cytoskeleton dynamics. As a GAP for ARF1 and ARF5, AGAP1 directly regulates AP-3-dependent protein trafficking in the endosomal-lysosomal system 1, distinguishing it from the related AGAP2 which regulates AP-1 recycling endosomes. Beyond canonical Arf regulation, AGAP1 functions through multiple molecular interactions: it binds directly to the kinesin-13 motor protein Kif2A, enhancing its ATPase activity and regulating microtubule-dependent cytoskeleton remodeling 2, and it controls subcellular localization of FilGAP to regulate cell migration and invasion 3. Germline AGAP1 variants cause neurodevelopmental disorders including intellectual disability, autism, and dystonia 4. Loss of AGAP1 function impairs endolysosomal trafficking, chr2 activating the integrated stress response and rendering cells hypersensitive to environmental cytotoxic stressors 4. In cancer, mutant p53 upregulates AGAP1 expression via hnRNPA2B1-mediated mRNA stabilization, promoting esophageal squamous cell carcinoma progression through enhanced exosome formation 5. AGAP1 variants also interact with bevacizumab treatment outcomes in cancer patients, suggesting predictive clinical utility 6.