MLYCD (malonyl-CoA decarboxylase) is a mitochondrial and peroxisomal enzyme that catalyzes the conversion of malonyl-CoA to acetyl-CoA and CO₂ 1, serving as a critical regulator of fatty acid metabolism. In mitochondria, MLYCD promotes fatty acid oxidation by removing malonyl-CoA, which normally inhibits carnitine palmitoyltransferase 1 (CPT1) and blocks fatty acid entry into mitochondria 2. This activity shifts cellular metabolism toward fatty acid catabolism and away from de novo lipogenesis, thereby regulating the metabolic balance between glucose and lipid oxidation in muscle [UniProt]. In peroxisomes, MLYCD degrades malonyl-CoA generated during beta-oxidation of odd-chain dicarboxylic fatty acids [UniProt]. MLYCD deficiency is a rare autosomal recessive disorder (malonic aciduria) characterized by developmental delay, hypotonia, and potential cardiomyopathy 3, with disease severity potentially linked to protein mislocalization rather than catalytic defects 4. Clinically, MLYCD downregulation promotes cancer progression in clear cell renal cell carcinoma and osteosarcoma by facilitating lipid accumulation 56, while MLYCD functions as a protective factor in periodontitis 7. Restoring MLYCD expression represents a promising therapeutic strategy to reprogram fatty acid metabolism in cancer and metabolic diseases 52.