The Periostin/BMP1 axis was involved in regulating the proliferation and osteogenic differentiation of SMSCs in TWIST1+/− mice, and targeting the Periostin/BMP1 axis repaired craniosynostosis in TWIST1+/− mice, providing an SMSC-based treatment strategy for craniosynostosis with potentially beneficial implications for clinical practice. Here, POSTN is linked to craniosynostosis.