PTPRJ (protein tyrosine phosphatase receptor type J) is a receptor tyrosine phosphatase that functions as a multifaceted regulator of cellular signaling with both pro- and anti-angiogenic roles depending on context. The protein acts primarily through dephosphorylation of key signaling intermediates: it inhibits leptin signaling by dephosphorylating JAK2 at Y813 and Y868 sites 1, and suppresses EGFR signaling through mitochondria-dependent mechanisms involving the Rab21-MFN2-PTPRJ axis 2. PTPRJ regulates angiogenesis through interaction with syndecan-2, inhibiting endothelial cell migration and reducing active β1 integrin 3. In lung fibroblasts, PTPRJ activation via syndecan-2-derived peptides suppresses PI3K/Akt/mTOR signaling, reducing p62 accumulation and NF-κB-mediated profibrotic gene expression 4. In kidney disease, the Meis1/PTPRJ axis inhibits myofibroblast activation and renal fibrosis progression 5. Clinically, low PTPRJ expression correlates with improved outcomes in gastric cancer immunotherapy, associated with enhanced anti-tumor immune cell infiltration 6. Functionally, PTPRJ polymorphisms influence cancer susceptibility, with Arg326Gln variants associated with colorectal cancer risk 78. These findings establish PTPRJ as a potential therapeutic target in cancer, fibrotic diseases, and metabolic disorders.