The contactin associated protein-like 2 (CNTNAP2) gene has been implicated in autism spectrum disorder (ASD) and cortical dysplasia–focal epilepsy (CFDE) syndrome, which is characterized by seizures, language regression, intellectual disability, hyperactivity and autism. Now Daniel Geschwind and colleagues report the characterization of the mouse knockout of Cntnap2 (Cell 147, 235–246, 2011 ). Spontaneous seizures were seen in Cntnap2−/− mice older than 6 months of age. Cntnap2-deficient animals showed evidence of ectopic neurons in the corpus collosum and neuronal migration defects, similar to the pattern in patients with CDFE syndrome. The authors observed the knockout mice for behavioral abnormalities relevant to ASD and saw evidence of stereotypic motor movements and behavioral inflexibility. Knockout pups emitted fewer isolation-induced ultrasonic vocalizations, which are thought to be distress calls from pups to their mothers, and spent less time interacting with other mice in a juvenile play test. Risperidone is an FDA-approved drug for the alleviation of hyperactivity, repetitive behavior, aggression and self-injurious behaviors in ASD. Treatment of Cntnap2-deficient mice with risperidone led to lowered activity levels, repetitive grooming behaviors and perseveration, although no effect on social behavior was found. The authors suggest that the Cntnap2−/− mouse is an important new tool for assessing potential therapeutics in ASD.