,32,33 We find that Itgb3 haplo-insufficiency impairs network excitability and synchrony by limiting synaptic signaling of the metabotropic glutamate receptor mGluR5, which is similarly disrupted in fragile X syndrome (FXS), the most frequent monogenic form of ASD.34, 35, 36, 37 To assess the therapeutic potential of targeting Itgb3, we have implemented neuronal CRISPR activation (CRISPRa) systems that, unlike overexpression of exogenous β3 integrin, restored precisely β3 integrin protein levels to wild-type (WT) values both in vitro and in vivo. The gene discussed is GRM5; the disease is fragile X syndrome.