UMOD encodes uromodulin, the most abundant protein in human urine, exclusively produced by kidney tubule epithelial cells 1. Uromodulin functions as an antimicrobial agent by binding to bacterial type 1 fimbriae, particularly the fimH adhesin of E. coli, preventing pathogen attachment to urothelial receptors and facilitating bacterial clearance through urination 23. The protein also protects against multiple uropathogens including K. pneumoniae, P. aeruginosa, and S. mitis 3. Additionally, uromodulin contributes to urinary colloid osmotic pressure and inhibits crystal formation of supersaturated salts. Monoallelic UMOD mutations cause autosomal dominant tubulointerstitial kidney disease (ADTKD-UMOD), characterized by intracellular trafficking defects that lead to uromodulin entrapment in kidney cells, progressive renal dysfunction, and early-onset gout 45. Common UMOD variants are among the most significant loci associated with chr16 kidney disease across populations, affecting glomerular filtration rate and CKD risk 6. Genetic polymorphisms in UMOD also associate with increased renal stone disease risk, particularly when combined with metabolic abnormalities 7. Recent therapeutic approaches targeting TMED cargo receptors show promise in rescuing mutant uromodulin trafficking and reducing kidney damage 4.