The phospholipase A2 receptor (PLA2R) is a type I transmembrane glycoprotein related to the C-type animal lectin family such as the mannose receptor. PLA2R regulates a variety of biological responses elicited by secretory phospholipase A2s (sPLA2s). Group IB sPLA2 acts as an endogenous ligand to induce cell proliferation and lipid mediator production. Analysis of PLA2R-deficient mice suggested a potential role of the sPLA2-IB/PLA2R pathway in the production of proinflammatory cytokines during endotoxic shock. PLA2R is also involved in the clearance of sPLA2s, especially group X sPLA2, to protect their exaggerated reactions by potent enzymatic activities. In circulation, the soluble form of PLA2R is constitutively present as an endogenous inhibitor for mammalian sPLA2s.