Rapid and somewhat surprising advances have recently been made toward 
understanding the molecular mechanisms causing heritable disorders of 
hypophosphatemia. The results of clinical, genetic, and translational studies 
have interwoven novel concepts underlying the endocrine control of phosphate 
metabolism, with far-reaching implications for treatment of both rare Mendelian 
diseases as well as common disorders of blood phosphate excess such as chronic 
kidney disease (CKD). In particular, diseases caused by changes in the 
expression and proteolytic control of the phosphaturic hormone fibroblast growth 
factor-23 (FGF23) have come to the forefront in terms of directing new models 
explaining mineral metabolism. These hypophosphatemic disorders as well as 
others resulting from independent defects in phosphate transport or metabolism 
will be reviewed herein, and implications for emerging therapeutic strategies 
based upon these new findings will be discussed.