CMTM2 (CKLF like MARVEL transmembrane domain containing 2) is a transmembrane protein with diverse cellular functions across multiple organ systems. In male reproduction, CMTM2 is specifically expressed in testicular germ cells and sperm, where it localizes to the sperm middle piece and is positively correlated with sperm progressive motility 1. Reduced CMTM2 levels are observed in sperm from patients with asthenozoospermia and teratozoospermia, suggesting a critical role in sperm quality and function 1. In immune regulation, CMTM2 acts as a negative regulator of HIV-1 transcription by targeting AP-1 and CREB transcription factors 2. The protein functions as a tumor suppressor in hepatocellular carcinoma (HCC), where downregulation promotes epithelial-mesenchymal transition, cell proliferation, invasion, and metastasis [PMTM:32606785]. CMTM2 expression is significantly reduced in HCC tissues and correlates with tumor grade and poor prognosis 3. Additionally, serum CMTM2 levels serve as a potential biomarker for HBV-related disorders, with HBV infection suppressing CMTM2 expression through ubiquitin-proteasome degradation 4. CMTM2 has also been identified as an immune infiltration-related biomarker in Alzheimer's disease 5.