PZR (Protein zero related) is an immunoglobulin superfamily protein that specifically binds the tyrosine phosphatase SHP-2 through its intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs). PZR is phosphorylated by c-Src, c-Fyn, c-Lyn, Csk, and c-Abl. PP1, a Src family kinase inhibitor, inhibits PZR phosphorylation. There are three alternatively spliced isoforms designated as PZR, PZRa, and PZRb; both PZRa and PZRb lack ITIMs. PZR is a main receptor of ConA and has an important role in cell signaling via c-Src. PZR is expressed in many cell types and is localized to cell contacts and intracellular granules in BAECs and mesothelioma (REN) cells. Recently, PZR has been implicated as a cell adhesion protein that may be involved in SHP-2-dependent signaling at interendothelial cell contacts. Hypertyrosine phosphorylation of PZR was observed during embryogenesis in a mouse model of Noonan Syndrome.