Uromodulin: Functions in biogenesis and organization of the apical membrane of epithelial cells of the thick ascending limb of Henles loop (TALH), where it promotes formation of complex filamentous gel-like structure providing the water barrier permeability. May serve as a receptor for binding and endocytosis for cytokines (IL-1, IL-2) and TNF. Facilitates neutrophil migration across renal epithelia. Uromodulin, secreted form: Secreted into urine after proteolytical cleavage. Into the urine, may contribute to colloid osmotic pressure, retards passage of positively charged electrolytes, prevents urinary tract infection and modulates formation of supersaturated salts and their crystals.