Acyl-CoA synthetase long-chain family member 1 (ACSL1) is a key enzyme in lipid metabolism. It activates long-chain fatty acids to acyl-CoA esters, which are involved in multiple metabolic pathways such as fatty acid oxidation, re-esterification, and lipid signaling. ACSL1-related processes impact various biological functions like cell survival, energy metabolism, and response to oxidative stress [2,4,5].

In the context of diseases, in ovarian cancer, ACSL1 enhances antioxidant capacity and ferroptosis resistance by increasing the N-myristoylation and stability of FSP1 [1]. In the liver, TBK1 acts as a scaffolding protein to localize ACSL1 to mitochondria for fatty acid oxidation; liver-specific TBK1 knockout reduces fatty acid oxidation and causes fatty liver [2]. In diabetic nephropathy, downregulation of PRMT6 upregulates ACSL1 expression, leading to lipid peroxidation and ferroptosis [3]. In adipocytes, sortilin-mediated translocation of mitochondrial ACSL1 impairs thermogenesis and energy expenditure, and depletion of sortilin increases mitochondrial ACSL1 and activates beige fat [6].

In summary, ACSL1 plays crucial roles in lipid metabolism-related biological processes and is involved in multiple disease conditions such as cancer, fatty liver, and diabetic nephropathy. The use of gene-knockout models, like the liver-specific TBK1 knockout mouse model and the PRMT6-knockout mouse model, has significantly contributed to understanding ACSL1's functions in these disease contexts [2,3].