Uromodulin (UMOD) (UMOD)

Uromodulin (UMOD), historically known as Tamm-Horsfall protein, is a 85-95 kDa glycoprotein and the most abundant protein in human urine under physiological conditions [UniProt: P07911]. It is synthesized exclusively by the epithelial cells of the thick ascending limb (TAL) of the loop of Henle and is anchored to the luminal membrane before being proteolytically cleaved into the tubular lumen [PubMed: 28213613]. Biologically, uromodulin serves as a critical component of the innate immune system by binding to type 1 fimbriated Escherichia coli, thereby preventing bacterial adhesion to the urothelium [PubMed: 18033273]. It also regulates the activity of the NKCC2 transporter, influencing salt reabsorption and blood pressure, and acts as an inhibitor of calcium oxalate crystallization to prevent nephrolithiasis [PubMed: 24509544]. Mutations in the UMOD gene are linked to uromodulin-associated kidney disease (UAKD), where misfolded protein aggregates in the endoplasmic reticulum, leading to tubular injury and chronic kidney disease [PubMed: 30630773]. Current therapeutic interest focuses on uromodulin as a biomarker for nephron mass and as a target for preventing recurrent urinary tract infections and managing salt-sensitive hypertension.

Other names

Tamm-Horsfall proteinTHPUromucoidUromodulin

Uromodulin binds to type 1 fimbriated Escherichia coli to prevent bacterial adhesion to the urothelium and regulates the activity of the sodium-potassium-chloride cotransporter (NKCC2) in the thick ascending limb [PubMed: 18033273, 24509544].