MTR (methionine synthase) catalyzes the transfer of a methyl group from methylcobalamin (vitamin B12) to homocysteine, producing methionine in the cytosol 1. This enzyme functions as part of a multiprotein complex including MMACHC, MMADHC, and MTRR that safely delivers cobalamin to MTR for efficient methionine biosynthesis 1. The enzyme's cofactor, methylcobalamin, is regenerated by accepting a methyl group from 5-methyltetrahydrofolate, linking folate and cobalamin metabolism 1. MTR is essential for homocysteine metabolism and sulfur amino acid biosynthesis, with roles in nervous system development and axon regeneration 2. Mutations in MTR cause homocystinuria with megaloblastic anemia (cblG type), characterized by elevated homocysteine and methionine deficiency 3. The MTR A2756G polymorphism associates with increased male infertility risk and elevated homocysteine levels when combined with folate deficiency 4. However, this polymorphism shows no significant association with congenital heart disease or nonsyndromic cleft palate susceptibility 5. Neural tube defect risk involves complex interactions between MTR variants, folate status, and other homocysteine metabolism genes 6.