ACSS2 (acyl-CoA synthetase short-chain family member 2), also known as ACAS2, ACS, ACSA or AceCS, is a 701 amino acid cytoplasmic protein that belongs to the ATP-dependent AMP-binding enzyme family. Existing as a monomer, ACSS2 functions to catalyze the ATP-dependent activation of acetate, a reaction that yields acetyl-CoA for use in energy generation and lipid synthesis. ACSS2 expression, which is highest in liver and kidney tissue, is regulated by the presence of unsaturated fatty acids and sterol regulatory element-binding proteins (SREBPs). Human ACSS2 exists as two alternatively spliced isoforms and shares 93% sequence identity with its mouse counterpart, suggesting a conserved role between species.