KL and osteoporosis: Finally, Klotho knock-out mice, which are deficient in the prototypical FGF23 co-receptor alpha Klotho, exhibit signs of premature aging including typical age-associated diseases such as osteoporosis, impaired glucose tolerance and hearing loss in the presence of excessive phosphate serum levels.30 Taken together, tight control of systemic phosphate abundance is indispensable to vertebrate physiology.