KL and Osteopenia: The most notable clinical example is patients with tumoral calcinosis, a homozygous missense mutation of Klotho, accompanied by severe orofacial phenotypes, such as diffuse osteopenia and patchy sclerosis in calvariae as well as shortened roots.13 The latter was also observed in OsxCre;KLfl/fl mice under AP, highlighting the distinctive regulatory mechanisms of Klotho across different skeletal components.