Human NMO pathology and rodent models of NMO produced by passive transfer of anti-AQP4 autoantibody (AQP4-IgG) suggest a pathogenesis mechanism in which AQP4-IgG binding to AQP4 causes primary complement- and cell-mediated astrocyte toxicity, with a secondary inflammatory response leading to oligodendrocyte injury, demyelination, and axon loss. The gene discussed is AQP4; the disease is neuromyelitis optica.