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. Here, GPRASP2 is linked to autism.