ACOT1 (acyl-CoA thioesterase 1) is a cytosolic enzyme that catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A, thereby regulating intracellular levels of these metabolites 1. The enzyme shows substrate preference for saturated and unsaturated long-chain fatty acyl-CoAs (C12-C20) and plays a crucial role in fatty acid metabolism 1. ACOT1 functions as a protective factor against cellular damage by modulating lipid composition and preventing ferroptosis, a form of iron-dependent cell death characterized by lipid peroxidation 2. In cardiomyocytes, ACOT1 prevents doxorubicin-induced ferroptosis by shaping lipid composition, and its overexpression provides protection against this cell death pathway 2. However, ACOT1 downregulation is associated with increased susceptibility to ferroptosis in diabetic heart failure 3. The enzyme's expression is regulated by metabolic states, being downregulated during fasting in adipose tissue 4 and suppressed by FXR activation, which reduces fatty acid oxidation 5. Clinically, ACOT1 expression correlates with poor prognosis in gastric adenocarcinoma, where increased expression is associated with advanced tumor characteristics and decreased overall survival 6. The enzyme can also interact with environmental toxins like PFOA through specific amino acid residues 7.