RERG (RAS like estrogen regulated growth inhibitor) is a small GTPase tumor suppressor gene that functions as a negative regulator of cell proliferation and tumor growth. RERG binds GDP/GTP and possesses intrinsic GTPase activity, with higher affinity for GDP than GTP, similar to Ras family proteins but lacking prenylation signals and localizing primarily to the cytoplasm 1. The gene exhibits estrogen-responsive expression, being rapidly induced by β-estradiol in MCF-7 cells and repressed by tamoxifen 1. RERG demonstrates significant tumor suppressor activity through inhibition of anchorage-dependent and anchorage-independent cell growth in vitro and tumor formation in nude mice 12. In nasopharyngeal carcinoma, RERG suppresses cell proliferation, migration, and angiogenesis through the ERK/NF-κB signaling pathway 3. The gene shows gender-dependent expression patterns in hepatocellular carcinoma and is regulated by histone deacetylases 4. RERG expression is frequently lost due to promoter hypermethylation in various cancers including breast, kidney, ovary, colon, and nasopharyngeal carcinomas 235. This methylation-mediated silencing correlates with poor prognosis and aggressive tumor behavior, suggesting RERG loss contributes significantly to tumorigenesis across multiple cancer types 13.