Acyl-CoA synthetase long-chain family member 1 (ACSL1) is an enzyme that plays a crucial role in lipid metabolism. It activates long-chain fatty acids to their CoA derivatives, which are involved in various metabolic pathways such as fatty acid oxidation, re-esterification, and lipid signaling. ACSL1 is associated with multiple biological processes including cell survival, metastasis, and responses to oxidative stress [1-7]. Genetic models, like knockout (KO) or conditional knockout (CKO) mouse models, have been instrumental in studying ACSL1's function.

In ovarian cancer, ACSL1 promotes cell survival and peritoneal metastases. It enhances antioxidant capacity and increases ferroptosis resistance by modulating the myristoylation of FSP1, a ferroptosis suppressor 1 [1]. In the liver, TBK1 functions as a scaffolding protein to localize ACSL1 to mitochondria, regulating fatty acid oxidation. Liver-specific TBK1 knockout in mice reduces fatty acid oxidation and leads to fatty liver [2]. In adipocytes, sortilin-mediated translocation of mitochondrial ACSL1 impairs thermogenesis and energy expenditure. Depletion of sortilin in adipocytes increases mitochondrial ACSL1 and activates beige fat, preventing HFD-induced obesity and insulin resistance [3].

In conclusion, ACSL1 is essential in lipid metabolism-related biological processes. Studies using KO/CKO mouse models have revealed its significance in diseases such as cancer, fatty liver, and metabolic disorders. Understanding ACSL1's function provides insights into the underlying mechanisms of these diseases and may offer potential therapeutic targets.