CMTM7 is a transmembrane protein functioning as a tumor suppressor across multiple cancer types. Mechanistically, CMTM7 promotes Rab5 activation to facilitate receptor internalization and degradation 1, 2. In cancer cells, CMTM7 suppresses EGFR-AKT signaling by enhancing EGFR internalization 3, 1, and inhibits Wnt/β-catenin pathway signaling 4, 5. CMTM7 also promotes autophagy initiation through interaction with the ATG14L-Beclin1-VPS34 complex 6. In disease contexts, CMTM7 is frequently downregulated through promoter methylation and loss of heterozygosity in esophageal, gastric, pancreatic, liver, lung, cervical, and breast cancers 3. Ectopic CMTM7 expression induces G1/S cell cycle arrest, inhibits cell proliferation and motility, and suppresses tumor formation 3. Notably, CMTM7 regulates innate immunity: it inhibits TLR4 signaling in macrophages and provides protection against acute liver injury 2, while high expression correlates with M2 macrophage infiltration and immunosuppression in hepatocellular carcinoma 7. SOX10 acts as a transcriptional regulator of CMTM7 in gastric and pancreatic cancers 8, 4. These findings position CMTM7 as a multifunctional tumor suppressor with immunomodulatory properties.