Protein tyrosine phosphatases (PTPases) SHP-1 and SHP-2 are critical regulators in the intracellular signaling pathways that result in cell responses such as mitosis, differentiation, migration, survival, transformation or death. SHP-2 is a signal transducer for several receptor tyrosine kinases and cytokine receptors. A novel SHP-2 associated glycoprotein was recently cloned from human, rat, mouse and cattle by several labs and was designated SIRPalpha, SHPS-1, MyD-1, BIT and p84. SIRPalpha is a new gene family containing at least fifteen members. SIRPalpha is a substrate of many activated tyrosine kinases such as insulin receptor, EGFR, PDGFR and src, and a specific docking protein for SHP-2. SIRPalpha has regulatory effects on cellular responses induced by serum, growth factors, insulin, oncogenes, growth hormones and cell adhesion and plays a general role in different physiological and pathological processes.