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Inhibition of the enzymatic function and genetic deletion of DPP4 is associated with tremendous benefits to the heart, vasculature, adipose tissue, and the kidney in rodent models of obesity, diabetes and hypertension, and associated complications. The recently concluded, \u201cSaxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus\u2014Thrombolysis in Myocardial Infarction 53\u201d trial revealed a reduction in proteinuria in chronic kidney disease patients (stages 1-3). These results have spurred immense interest in the nonenzymatic and enzymatic role of DPP4 in the kidney. DPP4 is expressed predominantly in the glomeruli and S1\u2013S3 segments of the nephron and to a lesser extent in other segments. DPP4 is known to facilitate absorption of cleaved dipeptides and regulate the function of the sodium\/hydrogen exchanger-3 in the proximal tubules. DPP4, also known as CD26, has an important role in costimulation of lymphocytes via caveolin-1 on antigen-presenting cells in peripheral blood. 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