Prouroguanylin (about 9,7 kDa) is a biologically inactive form of uroguanylin circulating in a bloodstream. Uroguanylin is a small –molecular-weight peptide which has been shown to participate in the regulation of salt and water homeostasis in mammals via cGMP-mediated processes in the intestine, kidney and other epithelia. Prouroguanylin levels are markedly increased in chronic renal failure. The severity of chronic renal disease correlates with the magnitude of increases in plasma prouroguanylin concentrations. Uroguanylin/prouroguanylin levels also increased in the nephrotic syndrome. It may be concluded that uroguanylin/prouroguanylin is cleared from the circulation by the kidney and that reduced functioning renal mass and decreased glomerular filtration rates (GFR) lead to substantial increases in the concentrations of these peptides in serum and plasma. Circulating forms of uroguanylin and prouroguanylin are thought to be a major source of the urinary forms of biologically active uroguanylin. Both of these peptides can enter renal tubules by glomerular filtration. Prouroguanylin in the tubular lumen is than converted to active uroguanylin by tubular endoproteases because prouroguanylin is not detected in the urine. Studies of pathogenesis of colorectal cancer demonstrate that prouroguanylin may serve as marker of colon tumors in the body. Recent experiments also refer to possibility of prouroguanylin to play a significant role at diagnostic and treatment of heart diseases. Areas of investigation: Renal disease, Heart failure, Oncology