Because NCC is located at the apical membrane of the distal convoluted tubule of the nephron, it faces the lumen of the tubule and is in contact with the tubular fluid. Using the sodium gradient across the apical membrane of the cells in distal convoluted tubule, the sodium-chloride symporter transports Na+ and Cl− from the tubular fluid into these cells. Afterward, the Na+ is pumped out of the cell and into the bloodstream by the Na+-K+ ATPase located at the basal membrane and the Cl− leaves the cells through the basolateral chloride channel ClC-Kb. The sodium-chloride symporter accounts for the absorption of 5% of the salt filtered at the glomerulus. NCC activity is known to have two control mechanisms affecting protein trafficking to the plasma membrane and transporter kinetics by phosphorylation and de-phosphorylation of conserved serine/threonine residues.