PILR-alpha (paired immunoglobulin-like type 2 receptor-alpha; also named FDF03) is one of two members of a small family of immunoregulatory Ig-superfamily receptors. It is a counterpart to PILR-beta and it likely gave rise to PILR-beta through gene duplication and rearrangement. The PILRs represent one of many pairs of Ig-like domain-containing receptors that participate in immune regulation. PILR-alpha and -beta should not be confused with the similarly named PIRs (also paired immunoglobulin-like receptors), or the functionally-related SIRP and ILT/LILR/CD85/LIR family of receptors. While PIRs, ILTs and SIRPs contain three to six Ig-like domains in their extracellular region, PILR-alpha and -beta show only one Ig-like region in their extracellular domain (ECD). Mouse PILR-alpha is a monomeric, 271 amino acid (aa) type I transmembrane (TM) protein. It contains a 167 aa ECD, a 21 aa TM segment, and a long, 83 aa cytoplasmic region. The ECD shows one V-type Ig-like domain between aa 39-157, while the cytoplasmic region contains two ITIMs (immunoreceptor Tyr-based inhibitory motifs) between aa 265-270 and 294-299. Given that ITIMs are known to interact with phosphatases such as PTPN6 and PTPN11, the presence of these motifs makes mouse PILR-alpha an inhibitory receptor. In human, activation of PILR-alpha inhibits CD32/Fc gamma RII-induced calcium mobilization. Although CD99 is a known ligand for both PILR-alpha and -beta, highest affinity binding seems to occur between CD99 and PILR-alpha. Mouse PILR-alpha is found on neutrophils and macrophages. Mouse PILR-alpha ECD is 43% and 69% aa identical to human and rat PILR-alpha ECD, respectively; it is 75% aa identical to the ECD of mouse PILR-beta. One potential isoform of PILR-alpha has been reported. It varies only within the first 28 aa of the signal sequence.