Ptpn6, also known as SHP-1, is a protein tyrosine phosphatase that serves as a key regulatory protein in cellular signal transduction, playing a crucial role in controlling inflammation and cell death. It is involved in multiple pathways such as inhibiting myeloid differentiation primary response 88, enhancing the regulatory function of receptor-interacting protein kinase, and regulating necroptosis, apoptosis, and p38/mitogen-activated protein kinase pathways [1].

In Ptpn6-knocked out mice, inflammatory cytokines in white blood cells increased, leading to systemic and skin inflammation [1]. Ptpn6spin mice, with a single amino acid substitution in SHP1 proteins, develop an autoinflammatory disease. Ptpn6-deficient neutrophils in these mice, when transferred to Cd47-deficient mice, cause weight loss and death, which can be rescued by IL-1 blockade [2]. Concomitant deletion of Ptpn6 and Ptpn11 in T cells fails to improve T cell-mediated tumor control and even impairs the therapeutic effects of anti-PD1 treatment, with Ptpn6/11-deleted CD8+ T cells showing impaired expansion due to a survival defect [3].

In conclusion, Ptpn6 is essential in regulating inflammation and cell death processes. Studies using gene-knockout mouse models have revealed its role in inflammatory diseases like neutrophilic dermatosis and autoinflammatory diseases, as well as in the context of anticancer T-cell responses. Understanding Ptpn6's functions provides insights into potential therapeutic strategies for related diseases.