ARF1 is a small GTPase that functions as a master regulator of membrane trafficking and cellular homeostasis. Mechanistically, ARF1 recruits adaptor protein complexes to membranes to facilitate cargo selection and trafficking, with perinuclear ARF1 compartments mediating Golgi export while peripheral compartments regulate endocytic recycling 1. ARF1 also controls phosphatidylinositol 4-phosphate (PI4P) generation on trans-Golgi network vesicles, which drives mitochondrial division at endoplasmic reticulum contact sites 2. Additionally, ARF1 negatively regulates cGAS-STING signaling by maintaining mitochondrial integrity and promoting STING recycling; disease-associated ARF1 mutations impair these functions, causing type I interferonopathy 3. Clinically, ARF1 dysfunction is implicated in multiple cancers through distinct mechanisms: ARF1-mediated lipid metabolism sustains cancer stem cells, and ARF1 ablation induces anti-tumor immunity by triggering immune cell infiltration 4. Novel ARF1 inhibitors promote cancer stem cell aging and enhance anti-tumor immunity by expanding stem-like CD8+ T cells 5. In stroke, astrocytic ARF1 lactylation inhibition enables neuroprotective mitochondrial transfer from astrocytes to neurons 6. In obesity-related breast cancer, the SCARB2-ARF1-mTORC1 axis regulates glutathione-dependent tumor progression 7. These findings position ARF1 as a therapeutic target across multiple disease contexts.