Numerous genetic studies have reported an association between SHANK2 and autism spectrum disorders (ASDs). Won et al. generated mutant mice carrying a human ASD-associated microdeletion in Shank2. These mice exhibited a marked reduction in hippocampal NMDA receptor-mediated long-term potentiation and long-term depression and showed autistic-like behaviours (such as altered social interaction). Importantly, these behavioural deficits were attenuated by pharmacological modulation of metabotropic glutamate receptors that indirectly enhance NMDA receptor function, suggesting a possible future therapeutic approach for ASDs.