In this study we primarily sought to determine if ablation of the pyrophosphate generating enzyme, ENPP1, in TNAP null mice would rescue craniosynostosis and associated craniofacial skeletal abnormalities because deletion of ENPP1 in TNAP null mice was previously shown to rescue skeletal mineralization (13) and to further understand mechanisms that mediate the craniofacial abnormalities in hypophosphatasia. Here, ALPL is linked to craniosynostosis.