ACOT7 (acyl-CoA thioesterase 7) catalyzes hydrolysis of acyl-CoAs into free fatty acids and coenzyme A, with preferential activity toward palmitoyl-CoA but broad substrate specificity for C8-C18 fatty acyl-CoAs 1. The enzyme plays a critical physiological role in neurons by antagonizing fatty acid utilization, with loss of ACOT7 increasing neuronal fatty acid metabolism and exaggerating seizure susceptibility in both knockout mice and humans with genomic ACOT7 deletions 2. ACOT7 dysfunction also impairs systemic metabolic homeostasis, as Acot7-deficient mice on high-fat diets develop greater adiposity and glucose intolerance 2. Importantly, ACOT7 is upregulated across multiple malignancies including ovarian cancer, non-small cell lung cancer, gastric cancer, melanoma, and hepatocellular carcinoma, where it promotes tumor progression by suppressing ferroptosis and apoptosis while enhancing fatty acid synthesis and cell proliferation 34567. Transcriptional regulation of ACOT7 occurs through ARNTL2 and CREB1 in cancer contexts, while RNA modifications (N4-acetylcytidine) enhance ACOT7 mRNA stability 463. These findings establish ACOT7 as both a metabolic regulator critical for neurological and systemic homeostasis and an oncogenic driver warranting therapeutic targeting.