Neuron-specific Grip1/2-knockout mice show increased social interactions. Increased GluA2-pS880 in frontal cortex and decreased GABAβ3 expression in striatum were identified. Results support a role of Grip1/2-mediated AMPA signaling in regulating social behavior. Disturbances of AMPA- and GABA-signaling are implicated in autism social deficits.