In this context, the identification of a novel physiological mechanism that, in the inner medulla, links the activation of the CaSR by high urine Ca2+ levels to the regulation of the AQP2 expression and trafficking open new avenues for understanding AQP2 regulation and, consequently, how water balance is influenced by hypercalciuria (see schematic model in Figure 3). Here, CASR is linked to Hypercalciuria.