Neuropsychiatric symptoms in encephalitis and in lupus have been recognized and described for over 140 years, but we are only now in the twenty-first century finding reliable disease markers to categorize patients (1; 2). These markers have helped provide the first real world examples of precision medicine and bespoke therapies in brain autoimmunity. Autoimmune encephalitis, and N-methyl D-aspartate receptor (NMDAR) encephalitis in particular, currently lead the progress. The first realization that a systemic autoimmune disorder, systemic lupus erythematosus, affected the brain was that of Moriz Kapozi (1837–1902) in the 1870s. William Osler (1849–1919) described detailed case reports of young people with relapsing encephalopathies attributable to lupus (3). Lupus, like syphilis, is a great mimic. It has a range of subtle symptoms and can hide in plain sight. Brain involvement in lupus can be due to associated infarcts, sometimes with the added burden of the phospholipid syndrome; infection due to immune suppression agents or an intrinsic predisposition to infection; and a raised probability of developing autoimmune phenomena perhaps through autoantibodies, cytokines and innate mechanisms, though exact mechanisms still remain elusive in the 2020s (4).