SIAE is involved in the maintenance of immunological tolerance through negative regulation of Β-cell receptor (BCR) signaling. Recent evidences, though conflicting, indicate that rare loss-of-function SIAE variants are associated with susceptibility to various autoimmune diseases. Advances in understanding JIA pathophysiology have led to the consensus that systemic JIA (SJIA) is an autoinflammatory disorder while oligo/polyarticular JIA (O/PJIA) is an antigen-driven lymphocyte-mediated autoimmune disease.