MLYCD, or malonyl-CoA decarboxylase, is a key regulator of fatty acid anabolism. It catalyzes the conversion of malonyl-CoA to acetyl-CoA and carbon dioxide, thus regulating the disposal of malonyl-CoA from mitochondria and peroxisomes, and in the cytosol, its activity balances with that of acetyl-CoA carboxylase to regulate the malonyl-CoA pool [5]. This process is crucial for fatty acid metabolism, which is involved in many biological processes such as energy production and lipid synthesis.

In clear cell renal cell carcinoma (ccRCC), MLYCD is downregulated, and low expression correlates with poor prognosis. Restoring its expression in ccRCC cells blocks de novo fatty acid synthesis, promotes fatty acid oxidation, disrupts lipid homeostasis, and represses tumor progression. Overexpressing MLYCD also reduces tumor growth and reverses sunitinib resistance in vitro and in vivo. Mechanistically, HIF2α inhibits MLYCD translation [1].

In periodontitis, MLYCD is causally linked and serves as a protective factor [2]. Malonyl-CoA decarboxylase deficiency, caused by mutations in the MLYCD gene, is a rare autosomal recessive disorder. Patients may show developmental delay, hypotonia, and cardiomyopathy, among other symptoms. Diet and L-carnitine supplementation can be effective in some cases [3,4].

In osteosarcoma, MLYCD is downregulated, and overexpression effectively inhibits cell proliferation, migration, and invasion [6].

In conclusion, MLYCD is essential for fatty acid metabolism regulation. Its dysregulation is associated with diseases like ccRCC, periodontitis, and osteosarcoma. Studies on MLYCD-related gene knockout or deficiency models help understand its role in these diseases, potentially providing new therapeutic strategies for treatment.