RASSF1 (Ras association domain family member 1) functions as a tumor suppressor through multiple mechanisms. Structurally, RASSF1A mediates apoptosis by activating STK3/MST2 and STK4/MST1 kinases during Fas-induced cell death and promotes BAX-mediated mitochondrial apoptosis in response to TNF stimulation. The protein inhibits cell cycle progression at the G1/S-phase transition by negatively regulating cyclin D1 accumulation and interacts with CDC20 to inhibit anaphase-promoting complex activity, thereby restraining mitotic progression. RASSF1A also enhances p53-dependent checkpoint control by disrupting MDM2-DAXX-USP7 interactions. Clinically, RASSF1 inactivation through promoter methylation represents a hallmark epigenetic alteration across diverse malignancies. RASSF1 methylation occurs in 35% of pancreatic ductal adenocarcinomas 1 and is a well-characterized event in lung carcinoma 2. Meta-analysis of circulating tumor DNA demonstrates RASSF1 methylation achieves 97% specificity and shows diagnostic potential for cancer detection 3. RASSF1 promoter methylation is significantly associated with cervical cancer development and progression 4 and is notably elevated in SMARCB1/INI1-deficient sinonasal carcinomas 5. Pan-cancer analysis reveals reduced RASSF1 expression across 29 cancer types, correlating with poor overall survival in nine cancers including glioblastoma and lung cancer 6. RASSF1 expression significantly associates with immune checkpoint genes and tumor microenvironment composition, positioning it as both a prognostic biomarker and potential guide for immunotherapy selection.