Paired-immunoglobulin-like receptor (PIR) is a type I transmembrane protein, containing six Ig-like domains. Two isoforms (PIR-A and PIR-B) have been reported for this molecule. PIR-A/B is expressed on B cells, mast cells, macrophages, granulocytes, eosinophils, and dendritic cells. PIR-A requires association with FcRgammac for its cell surface expression and to act as an activating receptor. The ligand for PIR-A is MHC class I. PIR-B is an inhibitory receptor with 3 ITIM motifs on its cytoplasmic tail; when phosphorylated, they recruit the tyrosine phosphatases PTPN6/SHP-1 and PTPN11/SHP-2. MHC class I, Nogo, MAG, and OMgp are the ligands for PIR-B.