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. Author manuscript; available in PMC: 2023 Nov 1.
Published in final edited form as: Hypertension. 2022 Aug 12;79(11):2409–2418. doi: 10.1161/HYPERTENSIONAHA.122.18567

Figure 2: Pathways for Uromodulin release in the urine and circulation.

Figure 2:

Polymerizing uromodulin is targeted towards the apical membrane, where it is GPI anchored (inset). It is cleaved by hepsin at the consensus cleavage site, which releases the inhibitory external hydrophobic patch (EHP) site, thereby inducing conformational changes that allow the zona pellucida domains to polymerize. Non-polymerizing uromodulin is not cleaved by hepsin and is released in the urine without GPI anchoring. Non-polymerizing uromodulin is also the main form released from the basolateral domain to the kidney interstium and circulation