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Protein tyrosine phosphatase receptor gamma (PTPRG) is known to interact with and regulate several tyrosine kinases, exerting a tumor suppressor role in several type of cancers. Its wide expression in human tissues compared to the other component of group 5 of receptor phosphatases, PTPRZ expressed as a chondroitin sulfate proteoglycan in the central nervous system, has raised interest in its role as a possible regulatory switch of cell signaling processes. Indeed, a carbonic anhydrase-like domain (CAH) and a fibronectin type III domain are present in the N-terminal portion and were found to be associated with its role as [HCO3−] sensor in vascular and renal tissues and a possible interaction domain for cell adhesion, respectively. Studies on PTPRG ligands revealed the contactins family (CNTN) as possible interactors. Furthermore, the correlation of PTPRG phosphatase with inflammatory processes in different normal tissues, including cancer, and the increasing amount of its soluble form (sPTPRG) in plasma, suggest a possible role as inflammatory marker. PTPRG has important roles in human diseases; for example, neuropsychiatric and behavioral disorders and various types of cancer such as colon, ovary, lung, breast, central nervous system, and inflammatory disorders. In this review, we sum up our knowledge regarding the latest discoveries in order to appreciate PTPRG function in the various tissues and diseases, along with an interactome map of its relationship with a group of validated molecular interactors.

A Comprehensive Review of Receptor-Type Tyrosine-Protein Phosphatase Gamma (PTPRG) Role in Health and Non-Neoplastic Disease