ATP citrate lyase, also known as Acly or Acl, is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. The enzyme is composed of two polymer chains which are polypeptides in human. ATP citrate lyase is responsible for catalyzing the conversion of citrate and CoA into acetyl-CoA and oxaloacetate, along with the hydrolysis of ATP. A definitive role for ATP citrate lyase in tumorigenesis has emerged from ATP citrate lyase RNAi and chemical inhibitor studies, showing that ATP citrate lyase inhibition limits tumor cell proliferation and survival and induces differentiation in vitro. In vivo, it reduces tumor growth leading to a cytostatic effect and induces differentiation.