Dalia Rotstein, MD, MPH, St. Michael’s Hospital and the University of Toronto, Toronto, ON, outlines key research questions relating to AQP4-IgG seronegative neuromyelitis optica spectrum disorder (NMOSD). Considered more heterogenous than AQP4-IgG seropositive NMOSD, very little is known about seronegative NMOSD. Dr Rotstein highlights efforts to deepen our understanding of the etiology and pathophysiology of the disease and identify biomarkers to aid management. Given the rarity of seronegative cases, international collaboration will be critical to resolving many of the questions in this space. This interview took place at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) congress 2021.