CES1 (carboxylesterase 1) is a hepatic serine esterase that catalyzes the hydrolysis of ester and amide bonds in drugs and endogenous compounds 1. The enzyme activates ester prodrugs through hydrolysis of aromatic and aliphatic esters, with critical roles in xenobiotic detoxification and drug metabolism 2. CES1 plays a central role in reverse cholesterol transport by hydrolyzing cellular cholesteryl esters to free cholesterol, facilitating both initial efflux from macrophages and hepatic release of cholesterol for bile acid synthesis 3. The enzyme also metabolizes monoacylglycerides, 2-arachidonoylglycerol, and prostaglandins, and regulates triglyceride hydrolysis through SORT1-mediated protein turnover 4. Clinically, CES1 activity directly influences pharmacokinetics of multiple medications. Common genetic variants (e.g., G143E, L40T, G142E) can completely block enalapril metabolism, affecting angiotensin-converting enzyme inhibitor efficacy 5. The CES1 rs2244613 polymorphism significantly impacts dabigatran pharmacokinetics and bleeding risk, with T allele carriers showing higher drug concentrations 6. CES1 variants also affect clopidogrel, oseltamivir, and methylphenidate metabolism 2. Additionally, elevated CES1 expression correlates with hypercholesterolemia and increased CNS relapse risk in acute myeloid leukemia through immune cell modulation 7. Natural product interactions with CES1 may further alter drug disposition 8.