PTPRN (protein tyrosine phosphatase receptor type N) is a receptor-type protein expressed predominantly in neuroendocrine tissues, including pancreatic beta cells, brain, and other peptide-secreting cells. The protein functions through two distinct mechanisms: a nuclear form (ICA512-CCF) that enhances insulin gene expression by binding and stabilizing STAT5B phosphorylation, thus promoting beta-cell proliferation, and a cytoplasmic form (ICA512-TMF) that regulates insulin secretory granule dynamics by dimerizing with itself and displacing associated proteins to enhance granule exocytosis. Notably, PTPRN lacks functional tyrosine phosphatase activity despite its receptor-type PTP structure, having instead acquired specialized neuroendocrine regulatory roles during evolution. In type 1 diabetes, PTPRN serves as a major autoantigen; anti-PTPRN autoantibodies are detected in approximately 88% of newly diagnosed patients 1 and associate with disease progression in autoantibody-positive children 2. Beyond diabetes, PTPRN has emerged as a prognostic marker in glioblastoma (GBM). High expression correlates with poor survival outcomes and increased tumor aggressiveness 3. PTPRN promotes glioma cell proliferation and migration by activating the PI3K/AKT pathway through interaction with HSP90AA1 3, and appears in multiple independently constructed prognostic models for GBM 45. PTPRN knockdown reduces glioma cell growth and tumor development in xenograft models 3, positioning PTPRN inhibition as a potential therapeutic strategy, though no approved drugs currently target this pathway.