Homeostasis of inorganic phosphate (P_i) is primarily an affair of the kidneys. Reabsorption of the bulk of filtered P_i occurs along the renal proximal tubule and is initiated by apically localized Na⁺-dependent P_i cotransporters. Tubular P_i reabsorption and therefore renal excretion of P_i is controlled by a number of hormones, including phosphatonins, and metabolic factors. In most cases, regulation of P_i reabsorption is achieved by changing the apical abundance of Na⁺/Pi cotransporters. The regulatory mechanisms involve various signaling pathways and a number of proteins that interact with Na⁺/P_i cotransporters.