Lymphoid-tyrosine phosphatase (Lyp), encoded by the PTPN22 gene, is a member of the protein tyrosine phosphatase
family enzymes. Human genetics studies have shown that a single-nucleotide polymorphism in PTPN22 is often
mutated in patients suffering from autoimmune diseases such as type 1 diabetes, rheumatoid arthritis, and systemic lupus
erythematosis. Because of its critical role in the regulation of T-cell Receptor (TCR) signaling pathways, Lyp recently
emerged as a candidate target for therapy of autoimmune diseases. Herein, we review the structure and splice isoforms of
Lyp, the biochemistry of the disease-predisposing allele, discuss the function of the phosphatase in TCR signaling and the
association with human autoimmune diseases. Especially, we summarized recent progress in the development of Lyp
inhibitors, intending to provide a basis for the Lyp-based treatment of autoimmunity. Moreover, the emphasis and direction
for future study of Lyp in autoimmune diseases were prospected.
Autoimmune diseases, lymphoid-tyrosine phosphatase, Lyp, PTPs, inhibitor.
Department of Chemotherapy, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China.