IRE1α-XBP1s axis activation has been implicated in the pathogenesis of RA, by the demonstration that XBP1 splicing induces toll-like receptor-dependent cytokine secretion, which in turn induces XBP1 splicing in synoviocytes, in a autocrine loop that sustains synovial fibroblasts activation [47]. Here, ERN1 is linked to rheumatoid arthritis.