As such, the NPSLE attribution might change from the disease (SLE or not) to the related pathophysiology: anti-aquaporin-4 attribution, anti-N-methyl-D-aspartate receptor attribution, aPL attribution, anti-P ribosome attribution, anti-SSA attribution, etc. The holistic approach to each patient with NPSLE should be commenced, taking into account patients’ SLE-related conditions and comorbidities, the probable role of SLE physiopathology, and the need for specific treatment. This evidence concerns the gene AQP4 and systemic lupus erythematosus.