PTPRB (protein tyrosine phosphatase receptor type B) is a transmembrane receptor phosphatase essential for vascular endothelial function and tissue homeostasis. Mechanistically, PTPRB dephosphorylates critical endothelial signaling molecules including TIE2, VE-cadherin, and VEGFR-2, thereby negatively regulating angiopoietin-TIE2 signaling and controlling endothelial cell proliferation and vascular remodeling 12. The enzyme suppresses phosphorylation cascades downstream of TIE2, particularly the PI3K/AKT pathway, which is essential for angiogenesis 2. PTPRB dysfunction associates with diverse pathological conditions: reduced PTPRB expression in pulmonary fibrosis promotes endothelial-to-mesenchymal transition and fibroblast proliferation 1, while rare loss-of-function variants cause hypoplastic left heart syndrome through signal peptide defects affecting cardiac development 3. Conversely, PTPRB overexpression in colorectal cancer paradoxically promotes epithelial-mesenchymal transition and metastasis via TWIST1-dependent mechanisms 4, and elevated PTPRB expression in non-small cell lung cancer correlates with reduced Src phosphorylation and improved survival 5. Genetic variants in PTPRB associate with central serous chorioretinopathy, varicose veins, and glaucoma risk 6, and susceptibility to Graves' disease 7. These findings highlight PTPRB's context-dependent roles in vascular homeostasis and disease pathogenesis.