Since we have demonstrated that stimulating group I mGluRs upregulates FMRP through CREB (Wang et al., 2008a, 2009a, 2012a), it is likely that the downstream effect of this signaling pathway (group I mGluRs-CREB-FMRP) will be affected when FMRP is absent and thus cause alterations in synaptic responses in fragile X syndrome. The gene discussed is CREB1; the disease is fragile X syndrome.