This review will outline the role of FGF23 as a regulator of circulating phosphate levels via pathways involving its co‐receptor Klotho, activated vitamin D, and parathyroid hormone (PTH); the role of FGF23 in heart and kidney disease, hypophosphatemic rickets, and other conditions associated with FGF23 dysregulation; and lastly emerging therapeutics for treating FGF23‐mediated hypophosphatemia. This evidence concerns the gene KL and hypophosphatemia.