Uromodulin (UMOD)

Uromodulin (UMOD, also known as Tamm-Horsfall protein) is the most abundant protein in human urine and is exclusively produced by epithelial cells of the thick ascending limb (TAL) of the loop of Henle in the kidney[1][3][6]. It is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein, processed in the ER and Golgi with extensive N-glycosylation and formation of disulfide bonds, resulting in a mature protein of 640 amino acids. The structure features four epidermal growth factor (EGF)-like domains, a cysteine-rich region, and a bipartite zona pellucida (ZP) domain critical for its unique filamentous polymerization in urine. Uromodulin is cleaved from the cell membrane by the serine protease hepsin, which triggers filament assembly in a zig-zag fishbone-like arrangement. Its biological roles include protecting the kidney epithelium, regulating urine composition and volume, inhibiting formation of kidney stones, and aggregating urinary pathogens to aid their clearance. Genetic alterations in UMOD result in autosomal dominant kidney disease through cellular toxicity and impaired sodium/potassium transport. Uromodulin is increasingly recognized as a biomarker for kidney function and cardiovascular risk[1][2][3][5][6].

Other names

Tamm-Horsfall proteinTamm-Horsfall glycoproteinUromodulin, secreted formTHPUromucoidADMCKD2ADTKD1FJHNHNFJHNFJ1MCKD2THGP

Direct inhibition or stabilization of misfolded uromodulin (hypothetical, experimental); Indirect modulation through control of urinary concentration and handling of sodium/potassium (diuretics may indirectly interact)[5]