CMTM8 (CKLF-like MARVEL transmembrane domain containing 8) is a transmembrane protein that functions as a tumor suppressor across multiple cancer types. Structurally, CMTM8 encodes a protein with transmembrane 4 superfamily characteristics 1. Functionally, CMTM8 exhibits dual roles depending on cellular context: in mesenchymal stem cells, it promotes proliferation and migration through EGFR/ERK1/2 signaling while suppressing osteogenic differentiation 2; conversely, in cancer cells, CMTM8 overexpression inhibits proliferation, migration, invasion, and induces apoptosis 34. CMTM8 is significantly downregulated in multiple solid tumors including liver, lung, colon, rectum, esophagus, and stomach cancers, with expression inversely correlating with tumorigenesis 5. In bladder cancer specifically, CMTM8 downregulation associates with advanced tumor stage and grade, while restoration inhibits xenograft growth and metastasis 34. In colon cancer, CMTM8 serves as an EMT-immune-related prognostic biomarker negatively correlating with CD8+ T cell and dendritic cell infiltration 6. Genome-wide association data suggest CMTM8 involvement in alcohol dependence susceptibility 7. These findings position CMTM8 as a potential therapeutic target for cancer treatment and prognostic indicator for patient outcomes.