ACAT2 (acetyl-CoA acetyltransferase 2) is a membrane-bound enzyme that catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty acyl-CoA substrates, playing crucial roles in cellular cholesterol homeostasis 1. The enzyme exhibits tissue-specific transcriptional regulation by cholesterol, with increased ACAT2 mRNA expression and enzymatic activity observed upon cholesterol loading in human hepatoma cells 2. In monocytic cells, ACAT2 expression is regulated by C/EBP transcription factors and correlates with specific CpG hypomethylation patterns in its promoter region 3. Beyond cholesterol metabolism, ACAT2 demonstrates significant oncogenic functions through diverse mechanisms. In pancreatic cancer, histone lactylation drives ACAT2 transcriptional activation, which subsequently acetylates MTCH2 to disrupt oxidative phosphorylation and promote immunosuppressive cholesterol delivery via extracellular vesicles 4. In KRAS-mutant cancers, ACAT2 catalyzes GCLM lactylation, enhancing glutathione synthesis and conferring ferroptosis resistance 5. In gastric cancer, ACAT2 promotes proliferation and metastasis by upregulating SETD7, which prevents YAP1 ubiquitination and activates YAP1/TAZ-TEAD1 signaling 6. ACAT2 expression is decreased in unstable atherosclerotic plaques compared to stable plaques, suggesting protective vascular roles 7.