ACACB (acetyl-CoA carboxylase beta) is a mitochondrial enzyme catalyzing the carboxylation of acetyl-CoA to malonyl-CoA, a critical control point in fatty acid metabolism 1. The enzyme performs a two-step ATP-dependent reaction involving biotin carboxylation followed by carboxyl group transfer to acetyl-CoA 2. Through malonyl-CoA production, ACACB allosterically inhibits carnitine palmitoyltransferase 1, thereby suppressing fatty acid oxidation and promoting lipid storage 3. In hepatocellular carcinoma, ACACB dysregulation accelerates disease development; AMPK-mediated phosphorylation of ACC2 (Ser212) normally suppresses de novo lipogenesis, while loss-of-function mutations increase liver lesions 4. Conversely, ACC inhibition also increases hepatic gluconeogenesis by activating CPT-1-mediated fat oxidation and pyruvate carboxylase, revealing complex metabolic compensation 5. ACACB genetic variants associate with insulin sensitivity and adipose gene expression in humans 6, and rs2268388 links to diabetic nephropathy risk, elevated BMI, and increased hepatic triglycerides in obese populations 7. In cancer, ACC inhibition suppresses fatty acid synthesis required for tumor growth in non-small-cell lung cancer models 8, while PHD3-mediated ACC2 hydroxylation regulates exercise capacity through skeletal muscle fat oxidation 9.