Abstract: Irritability or aggressive conduct affects 25-50% of children with autism spectrum disorder (ASD). Despite being highly disruptive, aggression in the context of ASD is poorly understood due to a lack of good models. Deletions in PTCHD1 contribute to ~1% of ASD cases with intellectual disability and can lead to hyper-aggression. I will present our work seeking to understand the origin of hyper-aggression in a mouse model of Ptchd1 deletion. We are testing whether dysfunction of hypothalamic circuitry, and in particular the VMHvl is responsible for Ptchd1-mediated, ASD-related aggression. We find that specifically inhibitory circuitry and not excitatory contributes to hyper-aggression. In addition we will present preliminary findings on the cellular function of Ptchd1.