ACADL (acyl-CoA dehydrogenase long chain) is a mitochondrial enzyme that catalyzes the first step of long-chain fatty acid β-oxidation, converting acyl-CoA thioesters to trans-2-enoyl-CoA using electron transfer flavoprotein as an electron acceptor 1. The enzyme preferentially acts on saturated and unsaturated fatty acyl-CoAs with 6-24 carbons, with optimal activity on 8-18 carbon chains, and likely metabolizes bulky substrates including branched-chain fatty acids and sterol derivatives. ACADL is the predominant long-chain acyl-CoA dehydrogenase in lung type 2 alveolar epithelial cells, where it regulates surfactant production and controls alveolar inflammation 2. Functionally, ACADL plays a critical immunometabolic role: deleting Acadl in alveolar cells restricts neutrophilic inflammation during acute lung injury by reducing CXCL2 chemokine production 2. In hepatocellular carcinoma, ACADL functions as a tumor suppressor whose expression is mechanically regulated by extracellular matrix stiffness through the YAP/TEAD4 transcriptional axis 3. ACADL expression is also dysregulated in metabolic diseases: upregulated in non-alcoholic steatohepatitis livers and aberrantly regulated in diabetic cardiomyopathy hearts, contributing to lipid and branched-chain amino acid metabolic dysfunction 45. These findings establish ACADL as a metabolic hub integrating energy production, immune regulation, and tissue-specific physiological functions.