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Fragile X syndrome (FXS), the most common form of inherited mental retardation, is caused by the loss of functional fragile X mental retardation protein (FMRP). FMRP is an RNA–binding protein that can regulate the translation of specific mRNAs. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. In this study, we investigated whether Fmrp deficiency affects adult neurogenesis. We show that in a mouse model of fragile X syndrome, adult neurogenesis is indeed altered. The loss of Fmrp increases the proliferation and alters the fate specification of adult neural progenitor/stem cells (aNPCs). We demonstrate that Fmrp regulates the protein expression of several components critical for aNPC function, including CDK4 and GSK3β. Dysregulation of GSK3β led to reduced Wnt signaling pathway activity, which altered the expression of neurogenin1 and the fate specification of aNPCs. These data unveil a novel regulatory role for Fmrp and translational regulation in adult neurogenesis., Author Summary Fragile X syndrome, the most common cause of inherited mental retardation, results from the loss of functional Fragile X mental retardation protein (FMRP). FMRP is an RNA–binding protein and is known to bind to specific mRNAs and to regulate their translation both in vitro and in vivo. Adult neurogenesis, a process considered important for neuroplasticity and memory, is regulated at multiple molecular levels. Here we show that Fmrp could regulate the proliferation and fate specification of adult neural progenitor/stem cells (aNPCs). These data unveil a novel regulatory role for Fmrp in adult neurogenesis.