 fragile x syndrome ( fxs ) , the most common cause of inherited mental retardation and autism , is caused by transcriptional silencing of fmr1 , which encodes the translational repressor protein fmrp . 
 fmrp and cpeb , an activator of translation , are present in neuronal dendrites , are predicted to bind many of the same mrnas , and may mediate a translational homeostasis that , when imbalanced , results in fxs . 
 consistent with this possibility , fmr1-/y cpeb/ double knockout mice displayed significant amelioration of biochemical , morphological , electrophysiological , and behavioral phenotypes associated with fxs . 
 acute depletion of cpeb in the hippocampus of fmr1 -/y mice rescued working memory deficits , demonstrating reversal of this fxs phenotype in adults . finally , we find that fmrp and cpeb balance translation at the level of polypeptide elongation . 
 our results suggest that disruption of translational homeostasis is causal for fxs , and that the maintenance of this homeostasis by fmrp and cpeb is necessary for normal neurologic function . 
Supplementary Material