ZSCAN18 is a zinc finger transcription factor that functions as a tumor suppressor through transcriptional regulation. As a DNA-binding transcription factor with RNA polymerase II-specific activity 1, ZSCAN18 acts as a nuclear protein involved in regulating genes critical for cell growth and survival. Mechanistically, ZSCAN18 suppresses cancer cell proliferation and self-renewal by binding to promoter regions and regulating downstream targets. In glioblastoma, ZSCAN18 overexpression down-regulates GLI1, a terminal component of Hedgehog signaling, thereby inhibiting cell proliferation and enhancing chemosensitivity to Temozolomide 1. In gastric cancer, ZSCAN18 acts as a transcription factor that promotes TP53INP2-mediated autophagy, suppressing tumor growth 2. DISEASE RELEVANCE: ZSCAN18 is frequently inactivated across multiple gastrointestinal and urogenital cancers through promoter hypermethylation. In colorectal cancer, ZSCAN18 methylation occurs in 71-92% of tumors with high diagnostic specificity 3. Similar hypermethylation patterns are observed in cervical cancer (77.8% of samples) 4, gastric cancer, pancreatic cancer, renal cell carcinoma (32% of tumors) 5, and hepatocellular carcinoma 6. CLINICAL SIGNIFICANCE: ZSCAN18 promoter methylation serves as a sensitive biomarker for cancer detection and prognosis evaluation. A diagnostic model incorporating ZSCAN18 methylation achieved AUC of 0.9421 in cervical cancer validation cohorts 4. ZSCAN18 represents both a diagnostic marker and potential therapeutic target for multiple cancer types.