ARFGAP1 is a GTPase-activating protein that catalyzes GTP hydrolysis of ADP-ribosylation factor 1 (ARF1), a critical regulator of membrane trafficking 1. By promoting ARF1 inactivation, ARFGAP1 enables dissociation of COPI coat proteins from Golgi-derived vesicles, facilitating vesicle fusion with target compartments 2. The protein localizes to the Golgi through hydrophobic motifs in its non-catalytic domain, with tissue-specific isoforms identified in brain and heart 2. Beyond ARF1, ARFGAP1 exhibits GAP activity toward ARL1 at the trans-Golgi network and regulates endosome-to-TGN retrograde transport 3. Recent studies reveal broader signaling roles: ARFGAP1 inhibits mTORC1 activation by preventing its lysosomal localization through membrane curvature-sensing motifs, functioning as an independent prognostic factor in pancreatic cancer 4. ARFGAP1 also regulates LRRK2 GTPase activity; the proteins interact reciprocally, with ARFGAP1 enhancing LRRK2 GTP hydrolysis while LRRK2 phosphorylates ARFGAP1 and inhibits its GAP activity 5. ARFGAP1 silencing rescues neurotoxic phenotypes induced by Parkinson's disease-associated LRRK2 mutations, suggesting therapeutic potential 5. Additionally, C9orf72 toxic species implicated in ALS specifically disrupt ARFGAP1-mediated retrograde Golgi-to-ER transport 6, implicating ARFGAP1 dysfunction in neurodegeneration.