Although in some neurological diseases autoantibodies against surface antigens are directly pathogenic (e.g. the acetylcholine receptor (AChR) in MG, some synaptic antigens like the N-methyl-d-aspartate receptor (NMDAR) in NMDAR-encephalitis, aquaporin-4 (AQP4) in neuromyelitis optica (NMO)), in others (like those seen in paraneoplastic neuropathies, multifocal motor neuropathy (MMN), or Stiff-Person Syndrome (SPS)), autoantibodies directed against intracellular antigens do not exert a direct pathogenic effect and may only be disease markers. This evidence concerns the gene AQP4 and neuromyelitis optica.