OPN plays numerous roles in immune-related diseases such as multiple sclerosis (MS), rheumatoid arthritis, lupus-related diseases, Sjögren syndrome, and colitis, and it also plays an important protective role in the immune response [86] and might contribute to MS lesions and NMO pathology because of the elevated production of OPN in cerebrospinal fluid [87,88]. This evidence concerns the gene SPP1 and rheumatoid arthritis.