ARFGAP3 is a GTPase-activating protein that regulates ADP-ribosylation factor 1 (ARF1) activity to control intracellular vesicular trafficking and protein transport 1. As a GAP for ARF1, ARFGAP3 catalyzes GTP hydrolysis on ARF1, facilitating dissociation of coatomer from Golgi-derived membranes and enabling membrane fusion 1. ARFGAP3 localizes to the trans-Golgi network, early endosomes, and perinuclear regions, where it plays essential roles in COPI coat assembly and cargo sorting 23. Its GAP activity is regulated by phospholipids and requires interaction with coatomer for catalytic function 14. Beyond canonical secretory pathway functions, ARFGAP3 regulates post-Golgi transport of the cation-independent mannose 6-phosphate receptor and endosomal trafficking through GGA adaptor protein regulation 3. ARFGAP3 also functions in Golgi-to-ER retrograde transport through overlapping roles with ARFGAP1 and ARFGAP2 5. Clinically, ARFGAP3 is an androgen-regulated gene that promotes prostate cancer cell proliferation and migration via paxillin interaction 6. Recent evidence reveals ARFGAP3 protects against skeletal muscle aging by promoting autophagy and mitochondrial function through Rab5a-mediated signaling pathways, identifying it as a potential therapeutic target for age-related muscle decline 7.