Mutations in the Jagged-1 (Jag1) or Notch2 genes cause Alagille syndrome in humans, an autosomal dominant disorder with characteristic skeletal manifestations, including osteopenia and high prevalence of fractures.8 Dominant-positive Notch2-activating mutations cause Hajdu–Cheney syndrome, which also has a strong skeletal phenotype.9 Interest in the role of the Notch pathway during bone development and healing has grown dramatically over the past decade, with the majority of experimental data gathered in mice. Here, NOTCH2 is linked to Osteopenia.