Since the first discovery of the mammalian ACC inhibitor CP-640186 in 2003 (Figure 1), a large amount of ACC inhibitors have been identified, some of which have even been approved in clinical trials for the treatment of glycolipid metabolic diseases, such as type 2 diabetes mellitus (T2DM) and non-alcoholic steatohepatitis (NASH).19–21. This evidence concerns the gene ACACA and metabolic disease.