ARL1 (ARF-like GTPase 1) is a small GTPase that functions as a key regulator of trans-Golgi network (TGN) organization and vesicular trafficking 1. As a GTP-binding protein, ARL1 recruits multiple effectors including golgins (golgin-97 and golgin-245), arfaptins, and Arf-GEFs to the TGN, where it modulates their activities 23. The protein achieves specific subcellular targeting of effectors through distinct conformational interactions with different binding partners, exemplified by its recruitment of the Arf-GEF BIG1 via the dimerization and cyclophilin binding domain 3. ARL1 regulates diverse cellular processes including endosomal-to-Golgi retrograde transport and anterograde secretory trafficking 45. The protein coordinates with arfaptins to maintain insulin secretion from pancreatic beta cells and participates in innate immunity, cell polarity, lipid droplet formation, and neuronal development 1. Notably, arfaptin-1 acts as a negative regulator of ARL1-mediated retrograde transport, suggesting formation of functionally distinct ARL1-containing complexes in separate TGN microdomains 5. ARL1 dysregulation associates with multiple pathological conditions. Differential expression and splicing of ARL1 correlates with abdominal aortic aneurysm progression 6, and the gene is linked to various cancers and infections, though specific mechanistic contributions remain incompletely characterized.