Paired immunoglobulin-like type 2 receptor alpha (PILRA)

Paired immunoglobulin-like type 2 receptor alpha (PILRA) is a cell surface inhibitory receptor encoded on human chromosome 7, belonging to the immunoglobulin superfamily[1][3]. PILRA contains intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that recruit phosphatases such as SHP-1 and SHP-2, attenuating immune cell activation. It is expressed on various innate immune cells, including monocytes, microglia, dendritic cells, and certain NK cell subsets. PILRA recognizes a broad array of O-glycosylated protein ligands from mucin-type proteins through a unique mechanism requiring simultaneous recognition of both sialylated O-linked sugar antigens (such as sialyl Tn) and their peptide backbones[2][3]. Functionally, PILRA regulates immune signaling by counterbalancing activation from its paired receptor, PILRB. It serves as an entry coreceptor for HSV-1, directly binding the viral glycoprotein B and facilitating virus–cell fusion and infection. In addition, genetic variants of PILRA are implicated in susceptibility to Alzheimer’s disease, likely via effects on microglial function and immune regulation[3]. PILRA’s structural and ligand recognition features make it a potential, though as-yet untargeted, therapeutic target for infectious, inflammatory, and neurodegenerative diseases.

Other names

PILRAFDF03Cell surface receptor FDF03Inhibitory receptor PILR-alphaPaired immunoglobin like type 2 receptor alpha

Inhibitory signaling via SHP-1 recruitment and tyrosine dephosphorylation (ITIM motif–mediated) Promotes viral entry via direct binding to HSV-1 glycoprotein B in a sialic acid–dependent manner Regulates immune cell activation and quiescence through ligand interactions on NK cells and microglia