While AQP4-Ab are potentially of high diagnostic and therapeutic relevance, a critical need exists to challenge the current clinical practice of AQP4-Ab testing, for the following reasons: (1) Due to the low incidence of AQP4-IgG-positive NMO, the vast number of patients currently tested for AQP4-Ab [107], the limited specificity of some diagnostic assays, and the insufficient number of controls included in almost all past studies, the ratio of false-positive to true-positive test results might be higher than generally expected. The gene discussed is AQP4; the disease is neuromyelitis optica.