Kristina A Simeone, PhD, Creighton University, Omaha, NE, explains the main lines of evidence supporting the role of orexin in epilepsy. Orexin is a small neuropeptide existing in the lateral hypothalamus, that projects to regions all over the brain. In relation to sleep, orexin functions as the wake trigger by projecting through the ascending reticular activating system, to stimulate attention and provide muscle tone. Orexin has also been observed to be involved in narcolepsy, insomnia, and other sleep disorders. Comorbid sleep disorders occur in approximately one-third of people with epilepsy, and sleep disturbance and seizures have a complex bidirectional relationship, where each can exacerbate the other. The link between epilepsy and orexin is further supported by the ability of drugs blocking the orexin receptor to reduce seizures, as well as treat insomnia, in animal models. This aligns with the fact that extensive sleep deprivation can promote seizures and worsen them. This interview took place at the European Epilepsy Congress (EEC) 2022.