1 in 68 children born in the United States meets the diagnostic criteria for Autism Spectrum Disorder (ASD), a psychiatric illness that shares a high comorbidity with intellectual disability (ID). Despite the high prevalence of ASD, there are currently no mechanism-based treatments available due to a lack of understanding of the pathophysiological processes in the brain that disrupt behavior in affected individuals. Identifying convergent molecular pathways involved in known genetic causes of ASD and ID may broaden our understanding of these disorders and help advance potential targeted treatments for ASD. Synaptic protein synthesis is essential for modification of the brain through experience and is altered in several genetically-defined disorders, notably fragile X (FX), a heritable cause of ASD and ID. Neural activity directs local protein synthesis via activation of metabotropic glutamate receptor 5 (mGlu5), yet the mechanism by which mGlu5 couples to the intracellular signaling pathways that regulate synaptic mRNA translation is poorly understood. In this dissertation, we show that manipulation of two novel targets, b-arrestin2 and glycogen synthase kinase 3a (GSK3a) are able to independently modulate translation downstream of mGlu5. Avoiding dose-limiting consequences and unwanted side effects of globally targeting mGlu5 signaling, pharmacological inhibition of these targets has the potential to provide significant advantages over first-generation mGlu5 inhibitors for the treatment of FX. Finally, we show that a mouse model of 16p11.2 microdeletion disorder, a polygenic disorder known to confer risk for ASD and ID in humans, shares common features of synaptic dysfunction downstream of mGlu5 with the Fmr1 KO mouse. Chronic administration of pharmaceutical agents previously shown to restore synaptic function in the Fmr1 KO mouse successfully corrected many biochemical, cognitive and behavioral impairments in 16p11.2 df/+ mice supporting the hypothesis that troubled translation downstream of mGlu5 may be a convergent point of dysfunction between these two genetically-defined disorders.