Finally, our finding that Irx3flox/flox/Irx5−/−/Osx-Cre+ mice have reduced osteoblastic mineralization indicates that IRX3 to IRX5 binding maintains an important role in Hamamy syndrome and understanding the role of IRX3 and IRX5 together will help provide insight into the roles of IRX proteins in other organs. This evidence concerns the gene IRX5 and Craniofacial dysplasia-osteopenia syndrome.