Although the exact mechanism driving Fgf23 secretion in Phex and Dmp-1-deficient models has remained elusive thus far, several lines of evidence suggest that increased circulating Fgf23 is a major pathogenetic factor in XLH patients and Hyp mice, leading to hypophosphatemia and subsequently impaired bone mineralization. This evidence concerns the gene FGF23 and X-linked hypophosphatemia.