Phospholipase A2 receptor 1 (PLA2R1) (PLA2R1)

Phospholipase A2 receptor 1 (PLA2R1) is a large transmembrane glycoprotein and a member of the mannose receptor family, primarily known for its high-affinity binding to various secretory phospholipases A2 (sPLA2) (UniProt P35368). It is expressed on the surface of podocytes in the kidney, where it facilitates the endocytosis and clearance of sPLA2 enzymes (Ronco & Debiec, 2012). PLA2R1 is the primary autoantigen in approximately 70-80% of cases of primary membranous nephropathy (PMN), a leading cause of nephrotic syndrome in adults (Beck et al., 2009). In this autoimmune context, the immune system's recognition of PLA2R1 leads to the production of circulating IgG4 autoantibodies that form in situ immune complexes on the podocyte surface (Francis et al., 2016). These complexes trigger complement activation, resulting in podocyte damage, basement membrane thickening, and severe proteinuria (StatPearls, 2023). While no drugs currently bind directly to PLA2R1 in clinical practice, the receptor is the central target of the immune response managed by B-cell depleting agents like Rituximab (PubMed, 2021). Monitoring anti-PLA2R1 antibody titers has become a gold standard for diagnosing the disease, predicting relapses, and assessing treatment efficacy (NIH, 2022).

Other names

M-type phospholipase A2 receptorPLA2-R180 kDa secretory phospholipase A2 receptorCLEC13CC-type lectin domain family 13 member C

Therapeutic strategies primarily involve the depletion of B-lymphocytes or the suppression of the broader immune system to halt the production of pathogenic autoantibodies that recognize the PLA2R1 protein, thereby preventing the formation of subepithelial immune complexes.