Fragile X Syndrome (FX), which is caused by a silencing of the FMR1 gene, is the most frequent monogenetic cause of syndromic autism spectrum disorder (ASD). Evidence from genetic and molecular studies has demonstrated that dysregulated synaptic protein synthesis downstream of metabotropic glutamate receptor 5 (mGluR5) contributes to the pathophysiology of FX and may be a common disruption in other genetic causes of ASD. This work has suggested a variety of therapeutic targets, one of the most promising being direct manipulation of mGluR5 activity. However, there is a concern that global manipulation of mGluR5 will also affect processes that are unrelated to autism pathophysiology, resulting in side effects that will sharply limit the utility of this approach.  Ideally, pharmacological treatments should specifically interfere with the signaling pathways that regulate protein synthesis leaving other arms of signaling unaffected.  In this study, we identify a novel target that is a critical link between mGluR5 activation and mGluR5-mediated protein synthesis and synaptic plasticity. Genetic reduction of this adapter protein in Fmr1-null mice is sufficient to correct many recognized deficits, including exaggerated protein synthesis and mGluR-LTD as well as many cognitive and behavioral impairments.  Thus, targeting this signaling pathway may be a way to specifically modulate dysregulated protein synthesis associated with ASD, potentially leading to the next generation of selective drugs for the treatment of ASD.