PILRA

Paired Immunoglobulin-Like Type 2 Receptor Alpha (PILRA) is a transmembrane inhibitory receptor belonging to the paired immunoglobulin-like receptor (PIR) family, with no widely accepted alternative aliases. Expressed primarily on myeloid cells (e.g., microglia, macrophages), PILRA exerts its inhibitory function by recruiting phosphatases like SHP-1/SHP-2 via its cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM). This interaction suppresses downstream signaling cascades, thereby dampening excessive immune responses and maintaining immune homeostasis.
PILRA signaling intersects with pathways regulating myeloid cell activation, such as the TLR4-NF-κB axis, where it restricts pro-inflammatory cytokine production. Dysregulated PILRA is linked to neurodegenerative diseases (e.g., Alzheimer’s disease, as it modulates microglial clearance of amyloid-β) and viral infections (e.g., HSV-1 entry, where PILRA acts as a co-receptor). Currently, drug development targeting PILRA is in early stages, focusing on antibodies or small molecules that either block its inhibitory function to enhance anti-tumor immunity or disrupt its viral co-receptor role.