Global Klotho KO mice challenged with a diet low in Ca2+, PO34−, and vitamin D show hypercalcemia, renal Ca2+ wasting, osteopenia, and intestinal Ca2+ hyperabsorption (Alexander et al., 2009), highlighting that the Ca2+ leak is likely a consequence of Klotho failing to anchor TRPV5 to the membrane. This evidence concerns the gene TRPV5 and Osteopenia.