DPP3 is a zinc-dependent aminopeptidase that primarily functions in protein metabolism and bioactive peptide degradation 1. It cleaves dipeptides from the N-terminus of substrates including angiotensin II, Leu-enkephalin, and Met-enkephalin, thereby regulating blood pressure and pain modulation 1. Localized primarily to the cytosol, DPP3 can be released into circulation where it acts as both a biomarker and active mediator of cardiovascular homeostasis 2. Clinically, elevated circulating DPP3 levels correlate with disease severity and mortality in sepsis, cardiogenic shock, acute coronary syndromes, and COVID-19 2. In sepsis, elevated DPP3 contributes to dysregulation of the renin-angiotensin-aldosterone system, attenuating angiotensin II production despite elevated renin 3. DPP3's enzymatic degradation of angiotensin II disrupts vascular tone and myocardial contractility, leading to hemodynamic instability 2. Beyond cardiovascular disease, DPP3 is upregulated in multiple malignancies including esophageal, breast, and other cancers, where it promotes cell proliferation, migration, and tumor growth while conferring chemotherapy resistance 456. Antibody-mediated DPP3 inhibition with Procizumab shows therapeutic promise in preclinical models and early clinical trials for septic cardiomyopathy 2.