Acetyl-CoA acetyltransferase, mitochondrial, also known as acetoacetyl-CoA thiolase, is an enzyme that in humans is encoded by the ACAT1 (Acetyl-Coenzyme A acetyltransferase 1) gene. Acetyl-Coenzyme A acetyltransferase 1 is an acetyl-CoA C-acetyltransferase enzyme. This gene encodes a mitochondrially localized enzyme that catalyzes the reversible formation of acetoacetyl-CoA from two molecules of acetyl-CoA. The ACAT1 enzyme has a few unique properties. First, it is activated by potassium ions binding near the CoA binding site and the catalytic site. This binding causes a structural change in the active site loop. Additionally, this enzyme is able to use 2-methyl-branched acetoacetyl-CoA as a substrate, making it a unique thiolase. ACAT1 is regulated at both transcriptional and translational levels. ACAT1 enzyme activity is enhanced ACAT1’s expression is promoted transcriptionally by leptin, angiotensin II, and insulin in human monocytes/macrophages. Insulin-mediated regulation also involves ERK, p38MAPK, and JNK signaling pathways.