The regulation and functions of <scp>ACSL3</scp> and <scp>ACSL4</scp> in the liver and hepatocellular carcinoma

Abstract Hepatocellular carcinoma (HCC) is a heterogeneous disease that often features dysregulated tumour lipid metabolism. ACSL3 and ACSL4 are two homologous long chain acyl‐coenzyme A synthetases (ACSL) preferentially catalyse the activation of monounsaturated polyunsaturated fatty acids, respectively. Both enzymes frequently overexpressed in HCC, multiple reports have implicated progression. Increased expression these isozymes cells can upregulate metabolism through de novo lipogenesis, acid β‐oxidation acyl remodelling membrane phospholipids. We describe subcellular functions hepatocytes, transcriptional, epigenetic post‐translational mechanisms underpinning their regulation. discuss evidence modulate hepatocarcinogenic signalling by oncoproteins, cell death apoptosis or ferroptosis, protein degradation ubiquitin‐proteasome pathway. In addition, we survey how knowledge this area may inform new approaches to diagnosis treatment HCC deepen our understanding metabolic reprogramming promote hepatic growth.