RAB40C is a small GTPase that functions as a substrate-recognition component of the ECS(RAB40C) E3 ubiquitin ligase complex, mediating ubiquitination and proteasomal degradation of target proteins. As a member of the Rab family, it regulates intracellular membrane trafficking by cycling between inactive GDP-bound and active GTP-bound states that recruit downstream effectors for vesicle formation and fusion. RAB40C specifically mediates ANKRD28 ubiquitination to inhibit protein phosphatase 6 complex activity and suppress focal adhesion assembly during cell migration, and negatively regulates lipid droplet accumulation in a GTP-dependent manner. RAB40C has emerging roles in cancer progression. In hepatocellular carcinoma, RAB40C recruits TRIM21 to stabilize EGFR through K63-linked ubiquitination, sustaining EGFR signaling and promoting cell growth and migration 1. In gastric cancer, RAB40C is a direct target of let-7a microRNA and mediates suppression of cell proliferation and tumorigenicity 2. In osteosarcoma, RAB40C downregulation is associated with improved overall survival 3. At the population level, RAB40C variants influence disease susceptibility: polymorphisms rs62030917 and rs2269556 are associated with increased lumbar disc herniation risk in the Chinese Han population 4. The artemisinin compound shows promise as a RAB40C-targeting agent in hepatocellular carcinoma models, reducing RAB40C expression and suppressing cancer cell viability.