In this study, we revealed tumor cell-intrinsic ATP6V0A1 as a novel and crucial factor promoting the absorption of exogenous cholesterol via a RABGEF1-dependent endosome mature pathway in CRC cells, leading to higher ER-derived cholesterol level and 24-OHC production and upregulated TGF-β1expression. The gene discussed is RABGEF1; the disease is neoplasm.