RAB27B is a small GTPase that regulates intracellular membrane trafficking by cycling between inactive GDP-bound and active GTP-bound states to recruit downstream effectors 1. Primary functions include controlling late endosomal homeostasis, including endosomal positioning, maturation, and secretion 2, and facilitating NTRK2/TRKB axonal anterograde transport through association with KLC1 1. RAB27B plays a critical role in multivesicular endosome docking and exosome secretion, with distinct mechanisms from its isoform RAB27A; silencing RAB27B redistributes MVEs toward the perinuclear region and inhibits exosome release 3. RAB27B has significant disease relevance in cancer and immune regulation. In myeloid leukemia, RAB27B controls NRAS palmitoylation and plasma membrane trafficking, regulating RAS signaling and leukemogenesis; its depletion abrogates mutant NRAS-driven progenitor growth and reduces myelomonocytic leukemia development 4. In pancreatic cancer, RAB27B overexpression promotes invasion, proliferation, and chemoresistance; its knockdown enhances cisplatin sensitivity 5. RAB27B also regulates immune escape in gliomas through PD-L1 sorting in extracellular vesicles 6 and breast cancer through TGF-β-mediated suppression of EV release and altered cargo composition 7. Clinical evidence links RAB27B expression to poor prognosis in acute myeloid leukemia and sensitivity to MEK inhibitors 4. Additionally, RAB27B has been identified as a candidate causal gene for depression through integration of proteomic and transcriptomic data 8.