This review discusses the critical roles of the E3 ubiquitin ligases cIAP1/2 in mediating cell death pathways induced by TNF and promoting abnormal proliferation of fibroblast-like synoviocytes in RA, emphasizing the importance of the BIRC3-mediated ubiquitination process and its potential as a therapeutic target. This evidence concerns the gene TNF and rheumatoid arthritis.