AVPR2 is an X-linked G protein-coupled receptor that mediates arginine vasopressin (AVP) signaling to regulate renal water reabsorption 1234. The receptor is coupled to Gs G alpha proteins and, upon AVP binding, activates adenylate cyclase to increase intracellular cAMP 34. In the kidney collecting duct, AVPR2 activation promotes aquaporin-2-mediated water reabsorption, enabling urine concentration and fluid homeostasis 56. Loss-of-function AVPR2 mutations cause X-linked nephrogenic diabetes insipidus (NDI), characterized by inability of kidneys to concentrate urine despite normal or elevated AVP levels, resulting in polyuria and polydipsia 57. Conversely, gain-of-function mutations cause nephrogenic syndrome of inappropriate antidiuresis with excessive water reabsorption 5. Clinically, desmopressin—a synthetic AVPR2-specific AVP analogue—effectively treats central AVP deficiency but is ineffective in nephrogenic forms 8. The receptor also functions in blood pressure regulation and hemostasis through vasopressin's systemic effects 910. Understanding AVPR2 mutations has provided molecular insight into vasopressin-regulated water transport mechanisms in kidney epithelium.