RASSF3 (Ras association domain family member 3) is a tumor suppressor protein located on chromosome 12.1 that encodes a 247 amino acid protein with a conserved Ras association domain 1. RASSF3 suppresses tumor formation primarily through p53-dependent mechanisms. The protein directly interacts with and facilitates ubiquitination of MDM2, the E3 ligase that targets p53 for degradation, thereby stabilizing p53 and promoting its accumulation 2. This stabilization leads to p53-dependent apoptosis and G1-S cell cycle arrest; RASSF3 depletion conversely impairs DNA repair after DNA damage and attenuates apoptotic responses 2, 3. RASSF3 is ubiquitously expressed in normal tissues but frequently downregulated in multiple human cancers 1. In non-small cell lung cancer, reduced RASSF3 expression correlates with progressive phenotypes including lymph node metastasis and increased cell migration 4. Promoter hypermethylation is a key inactivation mechanism in pituitary somatotroph adenomas 5 and represents a general silencing mechanism in sporadic tumors 6. Functional variants in RASSF3, particularly the rs6581580 T>G promoter SNP, modulate cancer susceptibility, with variant alleles associated with reduced head and neck squamous cell carcinoma risk 3. RASSF3 overexpression delays mammary tumor development in transgenic mouse models 7, establishing its therapeutic potential.