Abstract: “Pharmacoperones,” or Pharmacological chaperones correct the folding of misfolded proteins, allowing them to go throughout the cell's quality-control system and makes it correctly fold of a protein. In the distal convoluted tubule, and the collecting ducts of the kidney the vasopressin type 2 receptors (V2R) is present as a G protein-coupled receptor (GPCR), a seven-transmembrane protein. V2R normally responds to vasopressin and activates mechanism that concentrates urine and maintains water homeostasis. Mutation of the V2R which leads to mistrafficking of the receptor, which in turn results in vasopressin unresponsive cells. This insufficiency leads to nephrogenic diabetes insipidus (NDI). Recently, a novel aquaretic, Pharmacoperones - Tolvaptan, is a selective, competitive VPR2 antagonist used to target hyponatremia (low blood sodium levels) associated with congestive cardiac failure (CCF), cirrhosis, and the syndrome of inappropriate antidiuretic hormone (SIADH).