Acsm5, acyl-CoA synthetase medium-chain family member 5, is involved in fatty acid metabolism. It activates medium-chain fatty acids by converting them to acyl-CoA esters, which are important for processes like β-oxidation and lipid synthesis. This gene is associated with multiple biological pathways, and its dysregulation can have implications for various physiological and pathological conditions [2,4,5].

In the context of diseases, in ligamentum flavum (LF) hypertrophy, Acsm5 is significantly down-regulated. Overexpression of Acsm5 in LF cells in vitro inhibits free fatty acid (FFA)-induced lipid accumulation and fibrosis. In vivo in mice, it also inhibits LF thickening, lipid accumulation, and fibrosis, acting through the inhibition of the FABP4-mediated PPARγ signaling pathway [1]. In hepatocellular carcinoma (HCC), Acsm5 is down-regulated, and its overexpression in HCC cell lines reduces fatty acid accumulation, cell proliferation, migration, and invasion in vitro and inhibits tumor growth in mouse xenografts. DNA methylation by DNMT1 mediates the down-regulation of Acsm5 in this context [2]. In lumbar ligamentum flavum hypertrophy, hypermethylation of Acsm5, mediated by DNMT1, promotes the proliferation and fibrosis and inhibits the apoptosis of ligamentum flavum cells [3].

In conclusion, Acsm5 is crucial in regulating fatty acid metabolism. Through model-based research, especially in KO/CKO mouse models and in vitro cell experiments, it has been shown to play important roles in diseases such as LF hypertrophy and HCC. Understanding Acsm5 provides insights into the underlying mechanisms of these diseases, potentially leading to new therapeutic strategies targeting lipid metabolism and related pathways.