CES2 (carboxylesterase 2) is a Phase I drug-metabolizing enzyme that catalyzes the hydrolysis of ester, amide, and carbamate bonds in various pharmaceutical compounds and xenobiotics 1. The enzyme demonstrates broad substrate specificity, hydrolyzing drugs including aspirin and irinotecan, with distinct preferences compared to CES1 12. CES2 is primarily localized to major drug metabolism sites including the gastrointestinal tract, lungs, and liver, with significant inter-individual variability in expression 13. In human lungs, CES2 shows 8-15-fold inter-individual variation in activity, which is important for inhaled drug metabolism and prodrug activation 3. The enzyme undergoes age-dependent postnatal development, with significantly lower expression in infants younger than 3 weeks compared to older individuals, suggesting reduced metabolic clearance capacity in neonates 4. Clinically, CES2 genetic variants affect drug metabolism and outcomes, particularly for irinotecan and aspirin therapy 2. Multiple single nucleotide polymorphisms have been identified in the CES2 gene, including variants that alter amino acid sequences and splice sites, which may influence enzymatic function 5. The enzyme's role in converting prodrugs like irinotecan to active metabolites makes it therapeutically significant for cancer treatment applications 6.