PTPN22 is a protein tyrosine phosphatase that primarily functions as a negative regulator of T-cell receptor (TCR) signaling through dephosphorylation of key signaling molecules including LCK, FYN, ZAP70, and VAV 12. Beyond T-cell regulation, PTPN22 positively regulates toll-like receptor-induced type 1 interferon production 3 and modulates NLRP3 inflammasome assembly 4. Recently, PTPN22 was shown to negatively regulate platelet function by dephosphorylating phosphodiesterase 5A, with PTPN22 deficiency enhancing platelet aggregation and arterial thrombosis 5. Clinically, PTPN22 variants are strongly associated with autoimmune diseases. The rs2476601 SNP significantly increases rheumatoid arthritis risk across multiple populations, with odds ratios ranging from 1.69-2.79 depending on genetic model 6. PTPN22 polymorphisms also associate with susceptibility to type 1 diabetes, systemic lupus erythematosus, and Hashimoto thyroiditis 78. DNA hypermethylation of the PTPN22 promoter is significantly elevated in Hashimoto thyroiditis patients and correlates with thyroid volume 8. Additionally, PTPN22 variants interact with environmental factors like excessive fluoride exposure to modulate thyroid autoimmunity 9. PTPN22 represents both a therapeutic target for enhancing anti-tumor immunity and a key genetic risk factor for autoimmune disease 10.