The Complexities of Organ Crosstalk in Phosphate Homeostasis: Time to Put Phosphate Sensing Back in the Limelight

International audience; Phosphate homeostasis is essential for health and is achieved via interaction between thebone, kidney, small intestine, and parathyroid glands and via intricate processes involving phosphatetransporters, phosphate sensors, and circulating hormones. Numerous genetic and acquired disordersare associated with disruption in these processes and can lead to significant morbidity and mortality.The role of the kidney in phosphate homeostasis is well known, although it is recognized that thecellular mechanisms in murine models and humans are different. Intestinal phosphate transportalso appears to differ in humans and rodents, with recent studies demonstrating a dominant role forthe paracellular pathway. The existence of phosphate sensing has been acknowledged for decades;however, the underlying molecular mechanisms are poorly understood. At least three phosphatesensors have emerged. PiT2 and FGFR1c both act as phosphate sensors controlling Fibroblast GrowthFactor 23 secretion in bone, whereas the calcium-sensing receptor controls parathyroid hormonesecretion in response to extracellular phosphate. All three of the proposed sensors are expressedin the kidney and intestine but their exact function in these organs is unknown. Understandingorgan interactions and the mechanisms involved in phosphate sensing requires significant researchto develop novel approaches for the treatment of phosphate homeostasis disorders.