FMR1 and fragile X syndrome: To utilize the key role of the glutamatergic system in the understanding of the pathogenesis of FXS, the mGluR theory was postulated on the observation that activation of group I metabotropic glutamate receptors (metabotropic glutamate receptors subtypes 1 and 5 (mGluR1/5)) [27] is associated with dysregulated downstream signaling cascades [28] based on the loss of the regulation of translation in the absence of FMRP.