Aquaporin 2 (AQP2) is a channel protein found in the apical cell membranes and intracellular vesicles of the collecting ducts cells of the kidneys. In the plasma membrane, this protein forms a vasopressin-regulated water channel, which aids in the reabsorption of water. In the presence of vasopressin, a G-protein linked receptor causes the intracellular accumulation of protein kinase A, which in turn causes phosphorylation and subsequent activation of the aquaporin 2 protein. This activation enables the migration of the water channel to the apical membranes of the collecting duct cells, where they carry out the osmotic reabsorption of solute free water, thereby concentrating the urine for excretion.

About 10% of patients with inherited forms of Nephrogenic Diabetes Insipidus (NDI) have been found to carry mutations in the AQP2 gene. In these patients, deficiency of aquaporin 2 function leads to the excretion of highly dilute urine, resulting in severe dehydration and associated complications.

The AQP2 gene is located on the long arm of chromosome 12 at 12q13, where it spans a total length of 8kb. The gene belongs to the MIP/aquaporin family of genes, some of whose other members are also located at the same locus. AQP2 gene is made up of four exons, which together code for the protein made up of 271 amino acids, and weighing about 29 KDa. Structurally, the protein consists of six transmembrane helices and five loops, three of them extracellular. Phosphorylation of the Ser256 residue is necessary for the transfer of this protein to the plasma membrane, where it carries out its function.

As mentioned above, mutations in the AQP2 gene cause both autosomal dominant and recessive forms of NDI. The dominant mutations have been seen to cause retention of the mutated protein in the region of the endoplasmic reticulum, and prevent it from reaching its functional destination at the plasma membrane. Most of the recessive mutations also fall within this category. However, at least a couple of recessive mutations have been shown to result in proteins that although are properly targeted to the membrane, still remain non-functional.