Autoimmune diseases are a family represented by more than 100 cases of disorders. These illnesses affect about 3–5 % of the global population. Many factors influence autoimmunity, including gender (with a higher prevalence observed in women), genetic factors (for example, associations with Human Antigen Leukocytes (HLA) genes), and environmental factors (such as infections, tobacco smoke, and heavy metals). In some predisposed patients, a series of immune events finally lead to the production of autoantibodies directed against intra and extracellular antigens. One of the most important roles of the immune system is maintaining a balance between the immune response to pathogens and not triggering autoimmunity.[1], [2], [3], [4], [5] Loss of this control leads to failed tolerance mechanisms, which can result in the reaction to self-antigens and the production of autoantibodies and autoreactive B and T cells.[6] Autoantibodies can be detected in healthy individuals and appear transiently in different situations, i.e., after infections.[1], [2], [3] However, if they persist, in combination with other factors, they can lead to the development of chronic autoimmune diseases. One of these autoantibodies is an antibody directed against the protein TRIM21. This protein performs many important functions in the human immune system, including antiviral response. Anti-TRIM21 is one of the autoantibodies closely connected to the pathogenesis of SS or SLE. They are also commonly detected in a wide variety of other connective, autoimmune diseases, such as rheumatoid arthritis (RA), mixed connective tissue disease (MCTD), and idiopathic inflammatory myopathies (IIM).[4], [5], [7], [8]. Fig. 1, Fig. 2.

Due to its structure, the TRIM21 protein belongs to the TRIM (tripartite motif proteins) family. This group of proteins belongs to the E3 ubiquitin ligase family and is involved in a wide range of processes, including cell survival regulation and innate and antiviral responses.[3], [9].

This review aims to summarize current knowledge of the functions of TRIM21 in immunological processes, analyze the spectrum of TRIM21-associated diseases, and evaluate the clinical implications of anti-TRIM21 antibodies on the disease course.