PTPRZ1 is a transmembrane receptor protein tyrosine phosphatase with critical roles in neural development and disease. In the developing brain, PTPRZ1 is preferentially expressed in outer radial glia and regulates their proliferation and self-renewal through STAT3 signaling, supporting cortical expansion 1. PTPRZ1 mediates mitotic somal translocation, a developmental program reactivated in glioblastoma progression, where it promotes tumor invasion and is associated with PTPRZ1-MET fusion oncogenes 23. Beyond oncology, PTPRZ1 participates in the pleiotrophin-PTPRZ1-AKT signaling pathway in astrocytes, where reduced signaling contributes to depression-like behaviors; this pathway represents a potential therapeutic target for major depressive disorder 4. PTPRZ1 is highly expressed in glioblastoma stem cells and serves as a clinically actionable immunotherapy target, with successful development of CAR-T cells and TCR-T cells demonstrating antitumor efficacy 56. In clear cell renal carcinoma, PTPRZ1 stabilizes RNF26 protein through dephosphorylation, promoting TNF/NF-κB signaling and treatment resistance; PTPRZ1 inhibition enhances sensitivity to tyrosine kinase inhibitors and PD-1 blockade 7. Additionally, curcumin modulates PTPRZ1 activity to regulate RNA m6A modifications and reduce neuroinflammation 8.