ACSS2 also known as AceCS1 is a 701 amino acid cytoplasmic protein that catalyzes the ATP-dependent activation of acetate to form acetyl-CoA, a key substrate for energy production and lipid biosynthesis. This enzymatic activity maintains energy homeostasis and supports various metabolic pathways, particularly in tissues with high energy demands such as the liver and kidney, where ACSS2 expression is most abundant. ACSS2 is regulated by unsaturated fatty acids and sterol regulatory element-binding proteins (SREBPs), highlighting its importance in lipid metabolism and cellular signaling. Human ACSS2 exists as two alternatively spliced isoforms and shares 93% sequence identity with its mouse counterpart, indicating a conserved functional role across species.