ARF5 is a small GTPase belonging to the ADP-ribosylation factor family that regulates cellular membrane trafficking and protein transport. Primary function: ARF5 functions as an allosteric activator of cholera toxin's catalytic activity 1 and plays crucial roles in vesicular trafficking 1. Mechanism: ARF5 localizes to segregated nanodomains on the cis-Golgi, ER-Golgi intermediate compartments (ERGIC), and trans-Golgi network (TGN), where it recruits COPI coat proteins to regulate ER-Golgi bidirectional transport and post-Golgi sorting 2. ARF5 binds to the GORAB protein's IGRAB domain in its active GTP-bound state to facilitate Golgi targeting 3. RTK export from the endoplasmic reticulum requires simultaneous activation of ARF1, ARF4, and ARF5 4. Disease relevance: ARF5 is significantly overexpressed in 29 cancer types, with high expression in hepatocellular carcinoma (HCC) patients associated with poor overall survival, disease-free survival, and progression-free survival, suggesting an oncogenic role 5. ARF5 influences tumor immune infiltration and participates in energy-consuming cellular processes including protein synthesis and lipid metabolism 5. Clinical significance: ARF5 represents a potential biomarker for HCC diagnosis and treatment, and ARF inhibitors like brefeldin A and M-COPA may suppress cancer cell growth by blocking RTK trafficking 45.