TMEM196 (transmembrane protein 196) is a tumor suppressor gene with four membrane-spanning domains that plays a critical role in lung cancer suppression. Functionally, TMEM196 inhibits tumor cell growth by suppressing cell proliferation and migration while promoting apoptosis 12. Mechanistically, TMEM196 suppresses the Wnt/β-catenin signaling pathway by repressing β-catenin promoter transcription, thereby downregulating downstream metastasis-associated genes MMP2 and MMP7 2. TMEM196 expression is frequently lost in lung cancer through DNA hypermethylation (61.2-68.1% of primary tumors), which correlates with poor differentiation and advanced pathological stage 13. Clinically, TMEM196 hypermethylation serves as a non-invasive biomarker detectable in plasma (52.8%) and sputum (55.2%) samples, effectively distinguishing lung cancer patients from healthy controls (AUC=0.905) 3. Low TMEM196 expression independently predicts poor overall survival and shorter disease-free survival in lung cancer patients 13. Additionally, TMEM196 genetic polymorphisms (rs9886152, rs9639334, rs9638765, rs2097811) show protective associations against NSAID-exacerbated respiratory disease in asthmatic patients 4, suggesting broader immunological relevance beyond malignancy.