The lack of pathognomonic aquaporin 4 (AQP4) antibodies in seronegative NMOSD not only hinders early diagnosis, but also limits therapeutic options, in contrast to AQP4 antibody-positive NMOSD, where the therapeutic landscape has recently evolved massively.<h4>Case presentation</h4>We report a 56-year-old woman with bilateral optic neuritis and longitudinally extensive myelitis as the index events of a seronegative NMOSD, who was successfully treated with inebilizumab.<h4>Conclusion</h4>Treatment with inebilizumab may be considered in aggressive seronegative NMOSD. The gene discussed is AQP4; the disease is optic neuritis.