The hypothesis that phosphate metabolism was regulated by a secretory factor came from the clinical observation that patients with a phosphate-wasting disease could not be rescued by transplanting a healthy kidney, impling that the cause of phosphate-wasting might originate from another organ.108 The Fgf23 missense mutation was then identified in patients with autosomal dominant hypophosphatemic rickets (ADHR), an inherited disorder involving disturbed in phosphate homeostasis. Here, FGF23 is linked to autosomal dominant hypophosphatemic rickets.