The PTPN11 gene encodes SHP-2. a non-receptor protein tyrosine phosphatase critical for regulating intracellular signaling pathways, particularly the RAS/MAPK cascade, which governs cell proliferation, differentiation, and survival. SHP-2 contains two N-terminal SH2 domains that mediate protein interactions and a C-terminal catalytic domain responsible for its phosphatase activity. Dysregulation of PTPN11. often through gain-of-function mutations, is implicated in developmental disorders (e.g., Noonan syndrome, LEOPARD syndrome) and malignancies like juvenile myelomonocytic leukemia (JMML) and solid tumors. Antibodies targeting PTPN11/SHP-2 are essential tools for studying its expression, post-translational modifications, and signaling roles. They are widely used in techniques such as Western blotting, immunohistochemistry, and flow cytometry to assess protein levels, localization, and activation status in disease models or clinical samples. Additionally, these antibodies aid in identifying pathological mutations and evaluating therapeutic agents targeting SHP-2 in cancers. Research has highlighted SHP-2’s dual role as both an oncogenic driver and a tumor suppressor, depending on cellular context, making its precise detection vital for understanding disease mechanisms. The development of selective inhibitors and companion diagnostic antibodies remains an active area in precision oncology.