AQP4 antibody was known to be pathogenic, but for the lesion formation, the antibody should gain access to the CNS across the blood-brain barrier (BBB) with cellular/humoral immune factors.[1] There have been reported cases of long-term asymptomatic AQP4 antibody positive carriers, however, their initial events or mechanisms which could cause increased BBB permeability and NMOSD were not well understood.[2,3] Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by loss of motor neurons. The gene discussed is AQP4; the disease is amyotrophic lateral sclerosis.