BDNF mediates long-term potentiation (LTP) of hippocampal CA1 synapses by a translation-dependent mechanism. A master regulator of local protein synthesis at the synapse is fragile-X-messenger ribonucleoprotein (FMRP), however it is unclear to what extent FMRP mediates the effects of BDNF on the synaptic proteome. In this work we investigated whether FMRP regulates the synaptic content of GluN2B-containing NMDA receptors (NMDAR) with implication in synaptic plasticity. Acute hippocampal slices were prepared from WT and Fmr1y/- mice, and LTP was triggered with five theta-bursts, which induces BDNF release. Fmr1y/- mice showed an impairment in LTP of CA1 synapses, and blockade of BDNF-TrkB signalling further impaired LTP, while blocking GluN2B-containing NMDA receptors (NMDAR) was without effect. To dissect the underlying molecular mechanism, we knocked down (KD) Fmr1 expression in primary cultures of hippocampal neurons and analysed (i) BDNF-induced alterations in surface expression of GluN2B (sGluN2B), and (ii) the effect on Fmr1 KD on Pyk2 (regulator of synaptic NMDAR stability) and PSD95 (scaffold protein of the postsynaptic density), by immunocytochemistry. Fmr1 KD alone had no effect on synaptic sGluN2B and dendritic Pyk2 abundance, but abolished the upregulation induced by BDNF. Moreover, Fmr1 KD increased PSD95 immunoreactivity, a phenotype that was not observed after BDNF stimulation. Single particle tracking with quantum dots showed that FMRP downregulation does not impair BDNF-evoked decrease in lateral diffusion of synaptic GluN2B. Our data show a role for FMRP in BDNF-induced facilitation of glutamatergic synapses, probably exerted through Pyk2 and PSD95 translational control. (Supported by MSCA [ITN-#813986] and FCT)