MTHFR (methylenetetrahydrofolate reductase) catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, serving as a critical regulatory link between folate and methionine metabolic cycles 1. This enzyme maintains methionine and homocysteine balance essential for DNA, RNA, and protein synthesis and methylation 2. MTHFR functions as a key regulator of one-carbon metabolism, supporting cellular homeostasis 2. The common C677T polymorphism (p.Ala222Val), carried by approximately half the human population, reduces enzyme activity at body temperature and is the most prevalent cause of elevated homocysteine levels 23. This polymorphism's phenotypic impact depends on dietary folate levels and genetic background 3. Rare missense variants causing MTHFR deficiency represent the most common inherited folate metabolism disorder 3. Clinically, MTHFR polymorphisms associate with multiple conditions: the C677T variant increases ischemic stroke risk 4 and influences intracranial and cerebral hemorrhage susceptibility 5. Associations exist with rheumatoid arthritis 6, congenital heart disease 7, and childhood leukemia, where certain polymorphisms are protective 8. Elevated homocysteine from reduced MTHFR activity represents an independent cardiovascular disease risk factor 2. Vitamin B12 and folate supplementation can reduce plasma homocysteine levels and may prevent disease progression 9.