PTPN21 is a cytosolic non-receptor protein tyrosine phosphatase that regulates cellular processes through multiple signaling pathways and protein-protein interactions. As a phosphatase, PTPN21 dephosphorylates target proteins including the receptor tyrosine kinase ErbB4, thereby modulating downstream signaling cascades 1. Structurally, PTPN21 contains a FERM domain that serves as a protein-binding module, facilitating interactions with regulatory proteins such as KIF1C and Hook3 to relieve motor autoinhibition and activate intracellular transport 23. In disease contexts, PTPN21 exhibits context-dependent roles. Loss of PTPN21 disrupts mitochondrial homeostasis in lung epithelial cells, exacerbating experimental pulmonary fibrosis through increased reactive oxygen species and impaired autophagy, subsequently promoting fibroblast activation 4. Conversely, PTPN21 demonstrates pro-tumoral properties in cervical cancer, where it interacts with HPV18 E7 oncoprotein without undergoing proteasomal degradation, promoting cell migration and invasion 5. In acute lymphoblastic leukemia, the PTPN21-CDSlong isoform inhibits NK cell-mediated killing by downregulating HLA-I molecules 6. Therapeutically, PTPN21 shows neuroprotective effects in ischemic injury through ERK1/2-dependent cdk5 activation 7, and modulates bone marrow mesenchymal stem cell differentiation and immunosuppressive capacity 8.