Fig. 2.

A simplified illustration of the nephron focusing on the thick ascending limb of the loop of Henle (TAL) and the distal convoluted tubule (DCT). UMOD is depicted as being produced in TAL and DCT1 cells and secreted into the urine. Increased UMOD enhances sodium–potassium-chloride cotransporter (NKCC2) activity (via SPAR-OSR1), leading to greater reabsorption of sodium (Na⁺), potassium (K⁺), and chloride (Cl⁻). UMOD enhances sodium-chloride cotransporter (NCC) activity, increasing sodium and chloride reabsorption at DCT1. This results in increased blood volume and pressure, contributing to hypertension. ROMK regulates UMOD apical secretion in TAL. UMOD is also critical for maintaining magnesium homeostasis by regulating TRPM6 activity in the DCT