CMBL (carboxymethylenebutenolidase homolog) is a cysteine hydrolase enzyme localized to the cytosol and extracellular exosomes with hydrolase activity. While its endogenous physiological substrates remain unknown, CMBL functions as a critical enzyme for prodrug activation through xenobiotic metabolism. The enzyme catalyzes hydrolytic cleavage of dioxolone rings in ester-based prodrugs, yielding active metabolites, diacetyl, and CO2. CMBL specifically activates the angiotensin receptor blockers olmesartan medoxomil and azilsartan medoxomil into their pharmacologically active forms (olmesartan and azilsartan), making it essential for antihypertensive therapy efficacy. Additionally, CMBL can activate beta-lactam antibiotics including faropenem medoxomil and lenampicillin, expanding its clinical relevance to antimicrobial treatment. The enzyme's role in xenobiotic metabolism positions it as an important determinant of drug bioavailability and therapeutic efficacy. Understanding CMBL's substrate specificity and regulation is crucial for optimizing prodrug design and predicting inter-individual variability in drug response. Given its involvement in activating multiple therapeutic agents, genetic variations or altered expression of CMBL may influence clinical outcomes in patients receiving these medications, suggesting potential applications in personalized medicine and pharmacogenomics.