EPIDEMIOLOGY AND PREVENTION: Edited by Navdeep TangriUromodulin: more than a marker for chronic kidney disease progressionLaFavers, Kaicea; Garimella, Pranav S.b Author Information aDivision of Nephrology and Hypertension, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana bDivision of Nephrology and Hypertension, University of California San Diego, San Diego, California, USA Correspondence to Pranav S. Garimella, MD, MPH, Division of Nephrology and Hypertension, University of California San Diego, 9500 Gilman Drive, MC 7424, La Jolla, CA 92093, USA. Tel: +1 858 246 3294; e-mail: [email protected] Current Opinion in Nephrology and Hypertension 32(3):p 271-277, May 2023. | DOI: 10.1097/MNH.0000000000000885 Buy Metrics Abstract Purpose of review Uromodulin, a protein that is highly conserved across several species through evolution, functions to maintain homeostasis and prevent disease development and progression. Historically, the role of uromodulin has been thought to be limited to the kidney and genitourinary tract. This review highlights developments indicating a broader role of uromodulin in human health. Recent findings Although initially discovered in the urine and found to have immunomodulatory properties, recent findings indicate that serum uromodulin (sUMOD) is distinct from urine uromodulin (uUMOD) in its structure, function, and regulation. uUMOD binds pathogenic bacteria in the urine preventing infection and is also upregulated in kidneys undergoing repair after injury. Uromodulin knockout mice exhibit higher mortality in the setting of sepsis which is also associated with upregulation of sUMOD. sUMOD lowers calcification risk but this may be influenced by presence of kidney disease. Summary Uromodulin is an evolutionarily conserved protein produced exclusively in the kidney tubule cells with evolving roles being reported both in the kidney and systemically. Further research should be focused at harnessing its use as a potential therapeutic. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.