In this study, we found the new underlying mechanism whereby FGFR2 mutation p.Cys342Arg enhances mitochondrial metabolism-mediated osteogenesis through the FGF/FGFR-AMPK-Erk1/2 axis in Crouzon syndrome, which may provide a new adjuvant therapy for treating Crouzon syndrome. Here, MAPK3 is linked to Crouzon syndrome.