ARFRP1 is a trans-Golgi network (TGN)-localized small GTPase that regulates protein sorting and intracellular trafficking 1. As a member of the ARF family, ARFRP1 recruits the GTPase ARL1 to the TGN in complex with the transmembrane protein SYS1, initiating downstream trafficking cascades 2. Its N-terminal amphipathic helix mediates membrane association and subcellular localization independently of GTP binding, with N-terminal acetylation required for proper Golgi positioning 34. ARFRP1 controls multiple essential secretory pathways. In intestinal epithelium, it regulates chylomicron assembly and lipidation through interaction with Rab2 and ARL1, with ARFRP1-deficient mice showing reduced plasma lipids and growth retardation 5. In adipocytes, ARFRP1-dependent endosomal trafficking controls both adiponectin secretion and insulin receptor surface localization; its depletion impairs systemic glucose homeostasis 1. In pancreatic β-cells, ARFRP1 interacts with GOPC to regulate SNAP25 plasma membrane targeting, controlling both phases of glucose-stimulated insulin secretion 6. Additionally, ARFRP1 mediates Golgi-to-lysosome trafficking of SARS-CoV-2 envelope protein, affecting viral replication 7. ARFRP1 preferentially regulates anterograde TGN-to-plasma membrane transport, distinct from ARL1's role in retrograde endosome-to-TGN trafficking 8.