ACOT7 encodes an acyl-CoA thioesterase that hydrolyzes fatty acyl-CoAs (chain length C8–C18) into free fatty acids and coenzyme A, with preferential activity on palmitoyl-CoA, and has an important physiological role in the brain. The enzyme forms functional amyloid fibrils under physiological conditions while retaining catalytic activity 1. ACOT7 regulates neuronal activity and seizure susceptibility through fatty acid metabolism; loss of ACOT7 in mice results in increased seizure severity following kainic acid administration and metabolic complications including greater weight gain and glucose intolerance on a high-fat diet 2. In cancer contexts, ACOT7 is frequently upregulated and promotes tumor progression by suppressing ferroptosis and enhancing cell proliferation across multiple malignancy types. In ovarian cancer, the transcription factor NAT10 enhances ACOT7 mRNA stability through N4-acetylcytidine modification, promoting fatty acid metabolism and tumor progression; fludarabine inhibits this axis and suppresses ovarian tumorigenesis 3. Similar pro-tumoral mechanisms occur in non-small cell lung cancer, where the circadian factor ARNTL2 upregulates ACOT7 to promote cell proliferation and suppress apoptosis and ferroptosis 4, and in cutaneous melanoma, where CREB1 activates ACOT7 to enhance cell cycle progression and metastatic capacity 5. ACOT7 depletion enhances chemotherapy efficacy in breast and lung cancer cells through PKCζ-p53-p21 pathway activation 6, and USP3-mediated stabilization of ACOT7 drives cisplatin resistance in lung cancer via ferroptosis suppression 7.