Emerging roles of secreted phospholipase A2 enzymes: The 3rd edition

• This review updates the latest knowledge of sPLA2 functions in the past few years.
• sPLA2s regulate diverse biological events through unique lipid metabolism.
• Each sPLA2 displays unique substrate specificity, distribution, and functions.
• Novel in vivo roles of sPLA2s in immunity and metabolism are highlighted.
• PLA2R1 may act as a clearance or signaling receptor for sPLA2s in vivo.

Within the phospholipase A2 (PLA2) superfamily, secreted PLA2 (sPLA2) enzymes comprise the largest family that contains 11 to 12 mammalian isoforms with a conserved His-Asp catalytic dyad. Individual sPLA2s exhibit unique tissue and cellular localizations and specific enzymatic properties, suggesting distinct biological roles. Individual sPLA2s are involved in diverse biological events through lipid mediator-dependent or -independent processes and act redundantly or non-redundantly in a given microenvironment. In the past few years, new biological aspects of sPLA2s have been clarified using their transgenic and knockout mouse lines in combination with mass spectrometric lipidomics to unveil their target substrates and products in vivo. In the 3rd edition of this review series, we highlight the newest understanding of the in vivo functions of sPLA2s in pathophysiological conditions in the context of immunity and metabolism. We will also describe the latest knowledge on PLA2R1, the best known sPLA2 receptor, which may serve either as a clearance or signaling receptor for sPLA2 or may even act independently of sPLA2 function.