Fibroblast growth factor 23: state of the field and future directions

Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates and is regulated by blood levels of phosphate and active vitamin D. Post-translational glycosylation by the enzyme GALNT3 and subsequent processing by furin have been demonstrated to be a regulated process that plays a role in regulating FGF23 levels. In physiologic states, FGF23 signaling is mediated by an FGF receptor and the coreceptor, Klotho. Recent work identifying a role for iron/hypoxia pathways in FGF23 physiology and their implications are discussed. Beyond its importance in primary disorders of mineral metabolism, recent work implicates FGF23 in renal disease-associated morbidity, as well as possible roles in cardiovascular disease and skeletal fragility.