Fig. 1.

The illustration depicts the production of uromodulin by epithelial cells of thick ascending Loop of Henle (TAL). Human uromodulin, a 640-amino acid protein (top), undergoes extensive glycosylation and is anchored to the cell membrane via a GPI anchor. Following cleavage by the serine protease hepsin at the apical cell surface (right-side), uromodulin is secreted into urine, where it polymerizes to form the matrix of urinary casts. A smaller fraction of uromodulin is also released into the bloodstream through the interstitium, facilitated by the basolateral surface of the cells (left-side). The diverse functions of uromodulin, as depicted by circles in the figure, are complemented by the representation of single nucleotide polymorphisms on the UMOD gene, establishing its connection to hypertension in the illustrated bottom panel