FMRP loss of function causes Fragile X Syndrome (FXS) and autistic features. FMRP is a neuronal RNA-binding protein associated with polyribosomes, suggesting it regulates neuronal translation. This study uses HITS-CLIP to identify FMRP interactions with mouse brain polyribosomal mRNAs, revealing FMRP binds to coding regions of transcripts for pre- and postsynaptic proteins and autism-related genes. FMRP reversibly stalls ribosomes on its target mRNAs, suggesting that loss of translational control may contribute to FXS. The results provide insights into the molecular basis of cognitive and behavioral defects in FXS and ASD, and suggest multiple therapeutic targets. FMRP targets include genes involved in synaptic transmission and signaling, with significant overlap with autism susceptibility genes. FMRP binds to coding sequences and stalls ribosomes, suggesting a role in regulating translation during elongation. Loss of FMRP function relieves ribosome stalling, leading to increased protein synthesis. FMRP is associated with stalled ribosomes in a complex, and its interaction with mRNAs is confirmed by HITS-CLIP. The study highlights FMRP's role in synaptic plasticity and its potential as a therapeutic target for FXS and ASD. The findings suggest that FMRP regulates translation by stalling ribosomes on specific mRNAs, and its loss of function may lead to increased protein synthesis. The study provides a molecular basis for the overlap between FXS, autism, and synaptic plasticity, and supports the hypothesis that synaptic dysfunction is critical to the development of autistic features. FMRP targets include genes involved in synaptic function and signaling, and its interaction with mRNAs is confirmed by HITS-CLIP. The study also shows that FMRP is associated with stalled ribosomes in a complex, and its interaction with mRNAs is confirmed by HITS-CLIP. The findings suggest that FMRP regulates translation by stalling ribosomes on specific mRNAs, and its loss of function may lead to increased protein synthesis. The study provides a molecular basis for the overlap between FXS, autism, and synaptic plasticity, and supports the hypothesis that synaptic dysfunction is critical to the development of autistic features.FMRP loss of function causes Fragile X Syndrome (FXS) and autistic features. FMRP is a neuronal RNA-binding protein associated with polyribosomes, suggesting it regulates neuronal translation. This study uses HITS-CLIP to identify FMRP interactions with mouse brain polyribosomal mRNAs, revealing FMRP binds to coding regions of transcripts for pre- and postsynaptic proteins and autism-related genes. FMRP reversibly stalls ribosomes on its target mRNAs, suggesting that loss of translational control may contribute to FXS. The results provide insights into the molecular basis of cognitive and behavioral defects in FXS and ASD, and suggest multiple therapeutic targets. FMRP targets include genes involved in synaptic transmission and signaling, with significant overlap with autism susceptibility genes. FMRP binds to coding sequences and stalls ribosomes, suggesting a role in regulating translation during elongation. Loss of FMRP function relieves ribosome stalling, leading to increased protein synthesis. FMRP is associated with stalled ribosomes in a complex, and its interaction with mRNAs is confirmed by HITS-CLIP. The study highlights FMRP's role in synaptic plasticity and its potential as a therapeutic target for FXS and ASD. The findings suggest that FMRP regulates translation by stalling ribosomes on specific mRNAs, and its loss of function may lead to increased protein synthesis. The study provides a molecular basis for the overlap between FXS, autism, and synaptic plasticity, and supports the hypothesis that synaptic dysfunction is critical to the development of autistic features. FMRP targets include genes involved in synaptic function and signaling, and its interaction with mRNAs is confirmed by HITS-CLIP. The study also shows that FMRP is associated with stalled ribosomes in a complex, and its interaction with mRNAs is confirmed by HITS-CLIP. The findings suggest that FMRP regulates translation by stalling ribosomes on specific mRNAs, and its loss of function may lead to increased protein synthesis. The study provides a molecular basis for the overlap between FXS, autism, and synaptic plasticity, and supports the hypothesis that synaptic dysfunction is critical to the development of autistic features.