M-type phospholipase A2 receptor (PLA2R1)

The M-type phospholipase A2 receptor (PLA2R1) is a 180 kDa transmembrane protein belonging to the C-type lectin superfamily and the mannose receptor family. It primarily functions as a receptor for various secretory phospholipases A2 (sPLA2), mediating their clearance from the extracellular space and regulating downstream signaling pathways, including the MAPK cascade and p53-mediated cellular senescence. PLA2R1 is most clinically significant as the primary autoantigen in approximately 70–80% of patients with primary membranous nephropathy (PMN), an autoimmune kidney disease where circulating autoantibodies (predominantly IgG4) target the receptor on glomerular podocytes. This interaction leads to the formation of subepithelial immune complexes, complement activation, and subsequent podocyte injury and proteinuria. Beyond its role in renal pathology, PLA2R1 acts as a tumor suppressor by promoting apoptosis and senescence in response to oncogenic stress, and its downregulation is associated with enhanced tumor cell survival in several cancers. Current therapeutic strategies focus on depleting the B-cell populations responsible for producing anti-PLA2R antibodies, while the receptor itself serves as a critical diagnostic and prognostic biomarker.

Other names

Phospholipase A2 receptor 1PLA2RPLA2-RCLEC13CC-type lectin domain family 13 member C180 kDa secretory phospholipase A2 receptorM-type receptorPLA2G1R

B-cell depletion to reduce autoantibody production; non-specific immunosuppression to inhibit the autoimmune response against the receptor.