ACOT6 (acyl-CoA thioesterase 6) is a metabolic enzyme that catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A, thereby regulating intracellular lipid levels 1. The enzyme has specialized activity toward phytanoyl-CoA and pristanoyl-CoA, methyl-branched fatty acids derived from dietary phytol, and participates in both peroxisomal and cytosolic fatty acid metabolism pathways. Mechanistically, ACOT6 functions through acyl-CoA hydrolase activity to modulate fatty acid oxidation and metabolic homeostasis. In renal tubular cells exposed to calcium oxalate stress, ACOT6 activates the Akt/mTOR signaling pathway and suppresses apoptosis, protecting against crystal-induced cellular injury 1. This suggests ACOT6 plays a cytoprotective role beyond simple lipid catabolism. Clinically, ACOT6 expression alterations associate with disease states. ACOT6 was identified as a smoking-related molecular alteration in clear cell renal cell carcinoma, with candidate associations to ccRCC development 2. Additionally, ACOT6 was identified among six lipid metabolism-related genes with altered expression in synovial fluid of knee osteoarthritis patients with Yang deficiency and blood stasis syndrome, correlating with abnormal lipid metabolism in this condition 3. These findings suggest ACOT6 may serve as a biomarker and potential therapeutic target in metabolic-related pathologies.