PILR alpha is an immune inhibitory receptor possessing an immunoreceptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic domain enabling it to deliver inhibitory signals. Binding of PILR alpha to its ligand CD99 is involved in immune regulation; however, whether there are other PILR alpha ligands in addition to CD99 is not known. Here, we report that a novel molecule, PILR-associating neural protein (PANP), acts as an additional ligand for PILR alpha. Transcription of PANP was mainly observed in neural tissues. PILR alpha-Ig fusion protein bound cells transfected with PANP and the transfectants stimulated PILR alpha reporter cells. Specific O-glycan structures on PANP were found to be required for PILR recognition of this ligand. These results suggest that PANP is involved in immune regulation as a ligand of the PILR alpha. (C) 2011 Elsevier Inc. All rights reserved.