TMEM8B (transmembrane protein 8B), also known as nasopharyngeal carcinoma-associated gene 6 (NGX6), is a membrane-localized tumor suppressor protein that functions as a negative regulator of cancer cell growth and metastasis 1. TMEM8B operates through multiple interconnected mechanisms: it inhibits the EGF/Ras/MAPK signaling transduction pathway 2 and negatively regulates the Wnt/β-catenin signaling pathway 3. At the transcriptional level, TMEM8B overexpression suppresses AP-1 and Ets-1 expression while downregulating cyclin D1, thereby restraining cell cycle progression 4. TMEM8B expression is significantly reduced in multiple cancers including nasopharyngeal carcinoma, lung cancer, gastric cancer, liver cancer, and colorectal cancer, with particularly low levels in metastatic tumors 1. In hepatocellular carcinoma, reduced NGX6 expression correlates with advanced TNM staging and lymph node metastasis 5. Mechanistically, TMEM8B protein stability is regulated through a proteasome-dependent degradation pathway mediated by the cytoskeleton-linked protein ezrin, independent of ubiquitination 6. TMEM8B's expression is epigenetically controlled by promoter methylation and histone modifications 1, suggesting therapeutic targeting opportunities for cancer treatment.