Na⁺-K⁺-2Cl⁻ cotransporter (NKCC2) belongs to the family of integral plasma membrane proteins; solute carrier family 12 ,the electrically silent, cation-coupled chloride co-transporter family that mediates electroneutral symport of Na⁺, K⁺, and Cl⁻ with a stochiometry of 1:1:2, respectively. NKCC2 structure contains a central hydrophobic domain made up of 12 putative transmembrane spanning regions and a long hydrophilic loop connects transmembrane segments 7 and 8 and contains two glycosylation sites. The hydrophobic domain is flanked by a short amino- and a long carboxyl-terminal domain that are located within the cell.

NKCC2 encoded by the Slc12a1 gene shows at least six alternatively spliced variants and has the ability to form dimmers. NKCC2 activity and expression can be found in the medullary and cortical thick ascending limb of Henle's loop is the nephron and in macula densa cells.

NKCC2 allows Na⁺ and Cl⁻ entry from the tubule lumen into the thick ascending limb of  Henle's loop, a process that allows reabsorbing 25–30% of the NaCl filtered by the glomeruli. In addition, NKCC2 can sense luminal Cl⁻ concentration and initiates the signal for tubuloglomerular feedback in the specialized cells of the macula densa. Thus, NKCC2 activity is essential for salt conservation and for acute and chronic regulation of water balance.

Mutations in the human NKCC2 gene causes Bartter syndrome type 1 characterized by severe natriuresis hypercalciuria and magnesuria, the inability to concentrate urine, leading to hyponatremia, hypochloremia, metabolic alkalosis, and low blood pressure. Opposite to Bartter's syndrome, enhanced activity of NKCC2 NaCl is connected with human and animal hypertension.