Aim Fragile X mental retardation protein (FMRP) is an RNAbinding protein important for the control of translation and synaptic function.The mutation or silencing of FMRP causes Fragile X syndrome (FXS), which leads to intellectual disability and social impairment.γaminobutyric acid (GABA) is the major inhibitory neurotransmitter of the mammalian central nervous system, and its metabotropic GABAB receptor has been implicated in various mental disorders.The GABAB receptor agonist baclofen has been shown to improve FXS symptoms in a mouse model and in human patients, suggesting the role of GABAB receptor on FMRP regulation.Here we investigated the signaling events linking the GABAB receptor and FMRP.Methods Western blot was used in this study to detect protein expression and kinase phosphorylation in cerebellar granule neurons.For key molecules in signalling pathway, RNAi was used in MEFs to confirm the results in neurons.Results GABAB receptor activation upregulated cAMP response element binding proteindependent Fmrp expression in cultured mouse cerebellar granule neurons via two distinct mechanisms: the transactivation of insulinlike growth factor1 receptor and activation of protein kinase C.In addition, a positive allosteric modulator of the GABAB receptor, CGP7930, stimulated Fmrp expression in neurons.Conclusion These results suggest a role for GABAB receptor in Fmrp regulation and a potential interest of GABAB receptor signaling in FXS improvement.