GNMT (glycine N-methyltransferase) catalyzes the methylation of glycine using S-adenosylmethionine (AdoMet) to produce N-methylglycine (sarcosine) and S-adenosylhomocysteine, playing a crucial role in methyl group metabolism regulation 12. The enzyme functions as a key regulator of the methionine cycle by controlling the AdoMet/AdoHcy ratio, which is essential for maintaining cellular methylation status 3. GNMT exhibits protective effects against carcinogenesis by binding polycyclic aromatic hydrocarbons and inhibiting DNA adduct formation 4. The protein also interacts with novel binding partners including DEPTOR and NPC2, implicating it in mTOR signaling and cholesterol trafficking 4. GNMT deficiency is strongly associated with liver pathology, as knockout mice develop steatohepatitis and hepatocellular carcinoma (HCC) due to chr6 AdoMet deficiency 2. In human HCC, GNMT is frequently downregulated with loss of heterozygosity occurring in 36-47% of cases, suggesting it functions as a tumor suppressor 5. Polymorphisms in the GNMT promoter affect transcriptional activity and hepatic protein expression levels, with risk genotypes over-represented in HCC patients 3. Beyond cancer, GNMT may contribute to longevity by mimicking methionine restriction and activating autophagy pathways 1.