Aldose reductase (AKR1B1) is the first enzyme in the polyol pathway through which glucose is converted to sorbitol, and has been implicated in the etiology of diabetic complications. However, its physiological role is still not well understood. In the kidney, AKR1B1 is quite abundant in the collecting tubule cells and thought to provide protection against hypertonic environment. We report here that the mice lacking AKR1B1 showed hypercalcemia, hypercalcemia, hypermagnesemia, and reduced ability to concentrate urine, suggesting a new physiological role of AKR1B1 in divalent cation homeostasis.