The rapid and relatively unrestricted access of intravenously administered NMO-IgG to AQP4-expressing peripheral but not CNS tissues mandates the need for further investigation to explain the CNS specificity of NMO pathology and for development of creative strategies to promote access of NMO-IgG into the CNS to create animal models. The gene discussed is AQP4; the disease is neuromyelitis optica.