Acsl3, acyl-CoA synthetase long-chain family member 3, is an enzyme in the long-chain fatty acyl CoA synthetase (ACSLs) family. It contributes significantly to lipid metabolism by catalyzing the activation of long-chain fatty acids to produce acyl-coenzyme A, which is involved in fatty acid oxidation pathways. Dysregulation of Acsl3 has implications for various biological processes, making it an important gene for study, and genetic models such as KO or CKO mouse models can be valuable for understanding its functions [1,4,5].

In clear cell renal cell carcinoma (ccRCC), Acsl3 is essential for the metabolism of exogenous serum-derived lipids into lipid droplets, and its genetic or pharmacologic suppression is cytotoxic to ccRCC cells in vitro and reduces tumor weight in an orthotopic mouse model. Also, Acsl3 inhibition decreases ccRCC cells' susceptibility to ferroptosis, a non-apoptotic cell death involving lipid peroxidation [2].

In renal ischaemia-reperfusion injury, ANKRD1 promotes lipid peroxidation and ferroptosis by facilitating the degradation of Acsl3 via TRIM25-mediated ubiquitination, aggravating the injury, and attenuation of Acsl3 mitigates the anti-ferroptotic effect of ANKRD1 knockdown [3].

In breast cancer, ACSL3 expression is downregulated, and its knockdown promotes cell proliferation, migration, and epithelial-mesenchymal transition. ACSL3 suppresses breast cancer progression by impeding lipid metabolism reprogramming and inhibiting malignant behaviors through the phospho-YES1 mediated inhibition of YAP1 and its downstream pathways [4].

In conclusion, Acsl3 plays crucial roles in lipid metabolism-related biological processes. Model-based research, especially KO/CKO mouse models, has revealed its significance in diseases like ccRCC, renal ischaemia-reperfusion injury, and breast cancer. Understanding Acsl3's functions can potentially provide new therapeutic strategies for these diseases.