PTPRU (protein tyrosine phosphatase receptor type U) is a receptor-linked protein tyrosine phosphatase that regulates cell adhesion, proliferation, and differentiation through dephosphorylation of β-catenin 12. However, PTPRU is structurally unique among RPTPs as a redox-sensitive pseudophosphatase with two inactive phosphatase domains; despite lacking catalytic activity, it functions by competing with active phosphatases for substrate binding 3. PTPRU exhibits context-dependent roles: it negatively regulates osteogenic differentiation in quiescent mesenchymal stem cells while maintaining stemness 4, and is involved in neural development where miR-34c-5p targets its 3'UTR 5. In cancer, PTPRU shows paradoxical functions—while traditionally characterized as tumor-suppressive, nuclear-localized PTPRU isoforms promote gastric cancer and glioma progression through β-catenin and focal adhesion signaling 12. PTPRU alterations appear in prostatic basal cell carcinoma 6 and may modulate semaglutide's weight loss effects 7. These findings indicate PTPRU functions as a multi-isoform protein with tissue- and context-specific roles in development, homeostasis, and disease progression, potentially serving as a therapeutic target depending on disease context.