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Acetyl-CoA carboxylases (ACCs) are enzymes that catalyze the carboxylation of acetyl-CoA to produce malonyl-CoA¹. In mammals, ACC1 and ACC2 are two members of ACCs. ACC1 localizes in the cytosol and acts as the first and rate-limiting enzyme in the de novo fatty acid synthesis pathway². ACC2 localizes on the outer membrane of mitochondria and produces malonyl-CoA to regulate the activity of carnitine palmitoyltransferase 1 (CPT1) that involves in the β-oxidation of fatty acid. Fatty acid synthesis is central in a myriad of physiological and pathological conditions³. ACC1 is the major member of ACCs in mammalian, mountains of documents record the roles of ACC1 in various diseases, such as cancer, diabetes, obesity. Besides, acetyl-CoA and malonyl-CoA are cofactors in protein acetylation and malonylation, respectively, so that the manipulation of acetyl-CoA and malonyl-CoA by ACC1 can also markedly influence the profile of protein post-translational modifications, resulting in alternated biological processes in mammalian cells⁴. In the review, we summarize our understandings of ACCs, including their structural features, regulatory mechanisms, and roles in diseases⁵.