PLA2R1 encodes a receptor for secretory phospholipase A2 (sPLA2) that mediates diverse biological responses depending on cellular context. The receptor binds sPLA2-IB but not sPLA2-IIA, and also recognizes snake venom phospholipase A2-like toxins 1. In various cell types, sPLA2-IB binding activates signaling cascades including mitogen-activated protein kinases to promote cell proliferation and lipid mediator production; in neutrophils, it stimulates elastase release and cell adhesion. A soluble form of PLA2R1 circulates in plasma and negatively regulates sPLA2 function by blocking its biological activities. The receptor also exhibits endocytic properties, rapidly internalizing sPLA2 ligands to protect against their potent enzymatic activities. In podocytes, sPLA2-IB binding regulates cell survival and glomerular homeostasis. PLA2R1 is clinically significant primarily in primary membranous nephropathy (PMN), where circulating autoantibodies against PLA2R1 occur in 50–80% of patients 2. Anti-PLA2R1 antibody presence and elevated levels correlate with nephrotic syndrome severity and treatment response 3. The identification of PLA2R1 as a key autoantigen has enabled precision-based diagnosis and management: high or increasing anti-PLA2R1 antibody titers identify patients requiring immunosuppressive therapy. Rituximab, a B-cell-depleting agent, has emerged as first-line treatment for most PMN patients 2, fundamentally shifting therapy away from historical regimens combining corticosteroids with cyclophosphamide or calcineurin inhibitors.