RAB20 is a small GTPase that regulates intracellular membrane trafficking and plays critical roles in phagosome maturation and pathogen defense. In macrophages, RAB20 is upregulated by interferon-γ and controls phagosome maturation by inducing early delays and extending Rab5a and PI3P association with phagosomes 1. RAB20 maintains phagosome integrity and promotes endosomal membrane influx to control Mycobacterium tuberculosis replication within spacious proteolytic phagolysosomes 2. The protein also facilitates phagosome acidification and lysosome fusion, with deficiency leading to increased lysosomal injury and enhanced NLRP3 inflammasome activation in silicosis 3. RAB20 localizes to the Golgi apparatus and mitochondria, where it mediates hypoxia-induced apoptosis as a HIF-1 target gene 4 5. In hepatocellular carcinoma, RAB20 downregulation affects extracellular vesicle composition, reducing TPI1 content and promoting aerobic glycolysis that drives tumorigenesis 6. The gene is also overexpressed in pancreatic adenocarcinomas and regulated by Ikaros in B-cell acute lymphoblastic leukemia 5 7. These findings establish RAB20 as a key regulator of membrane trafficking with significant roles in immune defense, cellular metabolism, and cancer pathogenesis.