AQP2 is a vasopressin-regulated water channel protein expressed in renal collecting duct principal cells that forms a water-specific channel providing high permeability to water across the plasma membrane 1. This enables water movement along osmotic gradients, playing an essential role in renal water homeostasis and urine concentration 12. AQP2 is part of a brain-kidney regulatory axis: arginine vasopressin (AVP) secretion stimulates translocation of AQP2 from intracellular storage vesicles to the apical membrane via phosphorylation-dependent trafficking mechanisms, increasing water reabsorption capacity 34. Beyond AVP-dependent regulation, AQP2 expression is controlled by additional mechanisms including yes-associated protein, nuclear factor of activated T-cells, and prostaglandin E2 3. Mutations in AQP2 cause autosomal recessive or dominant nephrogenic diabetes insipidus (NDI), characterized by inability to concentrate urine despite normal AVP levels, resulting in polyuria and polydipsia 51. Most AQP2 mutations cause protein misrouting, preventing proper membrane localization 5. Abnormal AQP2 upregulation contributes to water retention disorders including congestive heart failure, hepatic cirrhosis, and syndrome of inappropriate antidiuretic hormone secretion 6. Early diagnosis and treatment of AQP2-related disorders can prevent serious complications including physical and mental retardation from recurrent dehydration 5.