MMADHC (metabolism of cobalamin associated D) is a cytoplasmic and mitochondrial protein essential for vitamin B₁₂ (cobalamin) metabolism and trafficking 1. It functions as a branch point protein that regulates the biosynthesis and proportions of two critical cobalamins: methylcobalamin (MeCbl) and 5'-deoxyadenosylcobalamin (AdoCbl) 2. MMADHC promotes oxidation of cobalamin bound to MMACHC and exploits cobalt-sulfur coordination chemistry at residues Cys-261 and Cys-262 to facilitate cofactor transfer to methionine synthase 3. Within the cytoplasm, MMADHC operates as part of a multiprotein complex with MMACHC, methionine synthase, and methionine synthase reductase that safely shuttles cobalamin to target enzymes 4. Pathogenic variants in MMADHC cause inherited cobalamin metabolism disorders (cblD type), presenting variable phenotypes including isolated or combined methylmalonic aciduria (MMA) and homocystinuria 1. Clinical MMADHC variants impair cofactor binding and off-loading, explaining the molecular basis of associated homocystinuria 3. These disorders are characterized by elevated methylmalonic acid and homocysteine, with disease severity correlating to the specific biochemical phenotype.