RAB7B is a small GTPase that controls vesicular trafficking from late endosomes to the trans-Golgi network (TGN). Beyond canonical membrane transport, RAB7B negatively regulates Toll-like receptor (TLR) signaling: it promotes lysosomal degradation of TLR9 and TLR4, suppressing inflammatory cytokine production in macrophages and dendritic cells 1. The protein also coordinates megakaryocytic differentiation through NF-κB-dependent interleukin-6 production. RAB7B localizes to lysosomal organelles and interacts with the GTPase-activating protein TBC1D5, which regulates its nucleotide cycle 2. Recent evidence reveals that RAB7B splice isoforms exhibit distinct subcellular localization and functions compared to the canonical Rab7a 3, and that RAB7B coordinates cytoskeletal organization by regulating RhoA activation and myosin II-mediated endosome dynamics 4. RAB7B dysfunction associates with inflammatory and metabolic disorders. In obesity models, RAB7B interacts with LRRK2 to suppress lysosomal degradation of lipid droplets; inhibition with ML282 blocks lipid accumulation in adipocytes 5. During colitis, RAB7B loss exacerbates TLR4-driven macrophage activation and intestinal inflammation, whereas synbindin stabilizes TLR4 degradation through RAB7B interaction 6. In cancer, RAB7B-mediated autophagy represents a therapeutic target; the natural product acetyl-11-keto-beta-boswellic acid inhibits oral squamous cell carcinoma growth by blocking autophagosome-lysosome fusion downstream of RAB7B 7. Emerging evidence indicates RAB7B homozygous variants can elicit off-target T-cell recognition in TCR-engineered therapies for KRAS-mutant tumors, raising safety considerations for cell immunotherapy development 8.