Using a combination of biochemical, electrophysiology, imaging and behavioural analysis, we show that GPRASP2 interacts and regulates mGluR5, that deletion of Gprasp2 alters synaptic communication and enhances mGluR-long-term depression (LTD) in hippocampal circuits, and that Gprasp2 knockout (KO) mice exhibit autism-like behaviours. The gene discussed is GRM5; the disease is autism.