PTPRT (protein tyrosine phosphatase receptor type T) is a brain-specific transmembrane protein that functions as a receptor-type tyrosine phosphatase with critical roles in neuronal development and cancer biology. In the nervous system, PTPRT regulates synaptic formation and neuronal development by forming homophilic trans dimers and heterophilic cis complexes with neuronal adhesion molecules 1. The protein dephosphorylates key substrates including BCR-Rac1 GAP and Syntaxin-binding protein, thereby controlling actin cytoskeleton polymerization and neurotransmitter release 1. PTPRT undergoes ADAM10- and γ-secretase-dependent cleavage, releasing an intracellular domain that translocates to the nucleus and regulates gene expression related to synapse formation and cell adhesion 2. In cancer, PTPRT functions as a tumor suppressor that is frequently mutated or downregulated across multiple cancer types 34. Loss of PTPRT enhances cancer cell proliferation, migration, and invasion through upregulation of survivin and other cell cycle-related genes 3. Paradoxically, PTPRT mutations predict enhanced response to immune checkpoint inhibitors by activating the STING pathway through prevention of STING proteasome degradation, leading to increased immune cell infiltration 54. PTPRT mutations are associated with cancer metastasis and serve as potential biomarkers for both prognosis and immunotherapy response 6.