ECH1 (enoyl-CoA hydratase 1) is a mitochondrial enzyme that catalyzes the isomerization of 3-trans,5-cis-dienoyl-CoA to 2-trans,4-trans-dienoyl-CoA, a crucial step in the β-oxidation of unsaturated fatty acids with double bonds at odd positions 12. The enzyme functions as a delta(3,5)-delta(2,4)-dienoyl-CoA isomerase, preparing unsaturated fatty acids for mitochondrial β-oxidation 12. ECH1's activity is regulated by TRAF3-mediated K63-linked ubiquitination at Lys214, which impedes its mitochondrial translocation and affects polyunsaturated fatty acid oxidation 2. The enzyme exhibits genetic polymorphism in humans, with two allelic variants differing in amino acid substitution (41 E→A) 3. ECH1 plays protective roles in multiple diseases: it alleviates nonalcoholic steatohepatitis by suppressing hepatic ferroptosis through inhibition of lipid peroxidation 4, reduces aortic valve calcification by suppressing Runx2 via Wnt5a/Ca2+ signaling 5, and acts as a tumor suppressor in hepatocellular carcinoma lymphatic metastasis 6. ECH1 deficiency creates metabolic vulnerabilities in metastatic cancer cells, making it a potential therapeutic target 1. Its expression is altered in various pathological conditions, suggesting roles beyond fatty acid metabolism in cellular stress responses and disease progression.