ARL8B is a small GTPase that primarily regulates lysosomal trafficking and positioning within cells. The protein functions by mediating the anterograde transport of lysosomes toward the cell periphery via kinesin-1 motors 1. ARL8B exhibits nucleotide-dependent localization, with ARL8B-GDP binding to lipid droplets through an exposed N-terminal amphipathic helix, while ARL8B-GTP predominantly localizes to lysosomes 2. This dual localization enables ARL8B to mediate contacts between lipid droplets and lysosomes, facilitating efficient lipid transfer and turnover 2. The protein also regulates lysosomal exocytosis, a process exploited by β-coronaviruses including SARS-CoV-2 for viral egress 34. In cancer contexts, ARL8B interacts with TRPML1 to trigger lysosomal exocytosis, which provides ferroptosis defense in AKT-hyperactivated cancers by reducing intracellular ferrous iron 5. Additionally, ARL8B influences the phosphorylation of Rab proteins by LRRK2, with perinuclear positioning of ARL8B-positive lysosomes promoting Rab10 phosphorylation 6. In hepatocellular carcinoma, elevated ARL8B expression correlates with poor prognosis and altered tumor microenvironment composition, while ARL8B knockdown causes lysosomal dysfunction leading to cell cycle arrest 7.