CMTM3 (CKLF-like MARVEL transmembrane domain containing 3) is a membrane protein with pleiotropic regulatory roles across immune, inflammatory, and oncogenic pathways. Primary function: CMTM3 acts as a tumor suppressor gene that is frequently downregulated in multiple cancer types including testicular, prostate, and gastric cancers 123. Mechanism: CMTM3 inhibits cancer cell proliferation, migration, and invasion through multiple signaling pathways. In cancer contexts, CMTM3 re-expression induces G2 cell-cycle arrest and apoptosis via p53 activation and caspase cleavage 1, and suppresses ERK1/2 phosphorylation 23. CMTM3 also stabilizes p53 protein by inhibiting proteasome-mediated degradation 4. In immune contexts, CMTM3 expression is elevated in sepsis and aggravates inflammation by promoting TLR4-dependent neutrophil activation and CXCR2-mediated recruitment 5. CMTM3 promotes colitis-associated carcinogenesis by stabilizing clathrin heavy chain, increasing vascular permeability through VE-cadherin downregulation 6. In cardiac tissue, CMTM3 deficiency induces hypertrophy via MAPK/ERK pathway activation 7. Disease relevance: CMTM3 dysregulation contributes to cancer progression, sepsis-induced organ damage, inflammatory bowel disease, and cardiac hypertrophy. Clinical significance: CMTM3 expression correlates with prognosis in gastric cancer and represents a potential therapeutic target for multiple diseases.