IRAP catalyzes the hydrolytic cleavage of the N-terminal residue in peptide substrates. Due to its active site plasticity and large binding pocket, it can hydrolyze substrates of various sizes. Some examples include the small linear peptide Met-enkephalin and large macrocyclic signaling peptides oxytocin and vasopressin. Especially important in this context is the cyclic neuropeptide oxytocin, a hormone known to positively affect human behavior and social functioning, and in childbirth where it plays a pivotal role initiating and maintaining uterine contractions during labor. IRAP has also been identified as the angiotensin type 4 (AT4) receptor: it binds the linear hexapeptide angiotensin IV, a metabolite of the hypertensive angiotensin II. Although the predicted binding mode of angiotensin IV to IRAP is almost identical to that of oxytocin, it is not hydrolyzed by IRAP; instead, it is a competitive inhibitor, with Ki in the high nanomolar range. It blocks the proteolytic activity of IRAP and so limits breakdown of natural substrates (see Figure for representative structures of oxytocin and angiotensin IV bound to IRAP, from molecular simulations). Due to their ability to inhibit IRAP, angiotensin IV peptide analogs and peptidomimetics are being used as scaffolds for development of inhibitors as pharmaceutical leads, which could potentially increase levels of peptide hormones in the brain and improve cognitive function such as learning and memory in pathological conditions such as Alzheimer's disease. Moreover, inhibition of IRAP has been shown to improve insulin sensitivity and glucose uptake in insulin-sensitive tissues, which makes IRAP promising target for the treatment of type 2 diabetes. The molecular structures of oxytocin and angiotensin IV are shown in Figure .