Exploring the ubiquitination regulatory network: opening new perspectives for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is a complex autoimmune disorder characterized by chronic systemic inflammation, primarily affecting the joints and synovium, but also involving multiple extra-articular tissues. This persistent inflammation contributes to progressive joint damage and the development of various systemic comorbidities. Despite significant advances in RA research, the underlying pathogenic mechanisms remain incompletely elucidated. Ubiquitination, a critical post-translational modification, regulates protein stability, localization, and function, and is essential in numerous biological processes, including cell signaling, immune regulation, and inflammatory responses. Emerging evidence highlights the pivotal role of ubiquitination in the pathogenesis of RA. This review provides a comprehensive overview of recent advances in the study of ubiquitination in RA, delineates its mechanistic contributions to disease development, and evaluates the therapeutic potential of targeting ubiquitination pathways. By offering new insights into RA pathophysiology, this review lays a theoretical and experimental foundation for the development of more effective, targeted therapeutic strategies, potentially opening new avenues for RA treatment.