Mammalian carboxylesterases (CES) are a well conserved family that catalyse the hydrolysis of a vast array of endogenous and exogenous substrates including environmental toxins and drugs. CES-mediated hydrolysis plays an important role in the disposition of a number of widely prescribed therapeutic agents from a diverse range of drug classes including angiotensin-converting enzyme inhibitors (ACEIs). In humans, two carboxylesterases, CES1 and CES2, are important enzymes in drug metabolism (Brzezinski et al. 1994, Pindel et al. 1997). Both are expressed in liver but levels of CE1 are much higher than CE2. Most ACEI prodrugs (except captopril and lisinopril) are administered as esterified prodrugs which are probably susceptible to hydrolysis by CES1 trimer (Thomsen et al. 2014). The resultant active drugs (suffix 'prilat') can inhibit the conversion of angiotensin I to angiotensin II, thereby contributing to the antihypertensive effect of these drugs. Some CES1 genetic variants (eg. G143E) may impair ACEI activation, and consequently affect therapeutic outcomes of ACEI prodrugs (Wang et al. 2016).