CCN2 has been demonstrated to display important roles in many cell types during the process of endochondral ossification and intramembranous ossification,13,14 two distinct processes of bone formation during embryogenesis in mammalian.46 Here, we also provide evidence that the requirement of CCN2 in early mesenchymal progenitor cells is potentially contributing to the molecular mechanism whereby CCN2 deficiency cause phenotypes observed in subject with SEMD. This evidence concerns the gene CCN2 and spondyloepimetaphyseal dysplasia.