Long-chain-fatty-acid–CoA ligase 1 (ACSL1)

Long-chain-fatty-acid–CoA ligase 1 (ACSL1) is an enzyme that catalyzes the activation of long-chain fatty acids by converting them into fatty acyl-CoA thioesters, an essential step for both lipid biosynthesis and fatty acid degradation through beta-oxidation[1][2][10]. ACSL1 exhibits high affinity for fatty acids with 16–20 carbons, such as palmitoleate, oleate, and linoleate, and is abundantly expressed in heart, liver, adipose tissue, and the nervous system[2][5][6]. It plays critical roles in metabolic homeostasis, including triglyceride synthesis, energy production, and myelination in the brain[2]. Dysregulation of ACSL1 has been implicated in multiple diseases, including cardiovascular disease, diabetes, obesity, atherosclerosis, neurological disorders, and several cancers, where either up- or downregulation can have pathophysiological effects[3][7][8]. ACSL1 function is also relevant for immune processes and is under investigation as a metabolic and disease biomarker. Deficiencies, mutations, or therapeutic targeting of ACSL1 impact key cellular energy and lipid pathways, which poses both therapeutic opportunities and safety challenges.

Other names

Acyl-CoA synthetase long chain family member 1ACS1FACL1FACL2LACSLACS1LACS2Long-chain acyl-CoA synthetase 1Long-chain acyl-CoA synthetase 2Long-chain fatty acid-CoA ligase 2Long-chain fatty-acid-coenzyme A ligase 1Palmitoyl-CoA ligase 1Palmitoyl-CoA ligase 2Phytanate–CoA ligaseLignoceroyl-CoA synthaseArachidonate–CoA ligaseFatty-acid-Coenzyme A ligase, Long-chain 1Fatty-acid-Coenzyme A ligase, Long-chain 2

Inhibition of ACSL1 blocks conversion of long-chain fatty acids into fatty acyl-CoA, thereby reducing lipid biosynthesis and beta-oxidation[2][3] Downregulation of ACSL1 limits triglyceride synthesis and ameliorates certain metabolic phenotypes[2][3]