Background: Inappropriate renal phosphate transport may alter serum phosphate concentration and bone mineralization, and it may also increase the risk of renal lithiasis or soft-tissue calcifications. Molecular identification of renal phosphate transporters and regulatory proteins has improved our knowledge of the mechanisms that control phosphate balance. This summary reviews recent findings regarding the consequences of mutations affecting several human genes encoding for phosphate transporters or regulatory proteins. Further, it describes the role played by the fibroblast growth factor 23–Klotho axis in phosphate homeostasis and its involvement in the pathophysiology of phosphate disturbances in chronic kidney diseases. Conclusions: This progress may allow development of new drugs that interfere with phosphate transporters, hormonal receptors or associated proteins to improve treatment and to help prevent secondary hyperparathyroidism.

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