CES5A (carboxylesterase 5A) is a serine hydrolase enzyme involved in xenobiotic detoxification and prodrug activation. The enzyme possesses characteristic catalytic features including a catalytic triad and oxyanion hole loop typical of carboxylesterase enzymes 1. CES5A is primarily expressed in kidney, with notable expression in liver and intestinal tissues important for drug metabolism and excretion 1. In males, CES5A shows epididymis-specific expression and has a functional requirement for male mouse fertility, suggesting reproductive tract-specific roles beyond its canonical metabolic functions 2. CES5A is detected in salivary proteomes across mammalian species with homology between human and canine proteins 3. Clinically, CES5A genetic variants interact with other drug-metabolism genes to influence platinum-based chemotherapy toxicity in non-small cell lung cancer patients; specifically, the ABCG2 rs2231142-CES5A rs3859104 interaction significantly associated with overall chemotherapy toxicity 4. Additionally, rare variants in CES5A were identified in genome-wide studies as contributing to amblyopia susceptibility, suggesting potential neurodevelopmental roles 5.