Fragile X syndrome (FXS), caused by FMR1 silencing, was modeled in common marmosets carrying FMR1 mutations. Mutants showed hyperactivity, seizures, and synaptic gene dysregulation, partially rescued by GRM5 mutation. F1 heterozygous females exhibited altered vocalization, social behavior, EEG, and motor deficits, providing a valuable translational model for FXS research and therapy.