CHMP4C (charged multivesicular body protein 4C) is a core ESCRT-III complex component with dual roles in endosomal trafficking and cell division. Canonically, CHMP4C mediates multivesicular body formation and cargo sorting into intraluminal vesicles for lysosomal degradation, and facilitates membrane fission during cytokinesis and viral budding 12. Beyond its ESCRT function, CHMP4C localizes to prometaphase kinetochores where it promotes stable kinetochore-microtubule attachments through NDC80 complex regulation and direct tubulin binding, supporting faithful chromosome 8 and mitotic checkpoint signaling 34. CHMP4C participates in the cytokinesis abscission checkpoint by binding VPS4A, preventing premature cell division 5. Clinically, CHMP4C is significantly overexpressed across multiple cancer types including pancreatic, lung, prostate, bladder, and breast cancer, correlating with poor prognosis 678910. In pancreatic cancer, elevated CHMP4C promotes progression by inhibiting necroptosis via the RIPK1/RIPK3/MLKL pathway and facilitating extracellular vesicle-mediated tumor-immune cell crosstalk 6. In bladder and prostate cancers, CHMP4C activates PI3K/AKT signaling to enhance proliferation and migration while suppressing apoptosis 98. CHMP4C overexpression also mediates chemotherapy resistance in breast cancer by targeting Snail 10, suggesting therapeutic targeting potential.