RIPK1 prevents aberrant ZBP1-initiated necroptosis

Receptor interacting protein kinase 1 (RIPK1) regulates inflammation and cell death, in host defense and homeostasis.The adaptor function of RIPK1 allows pro-survival and inflammatory signaling, while its kinase activity regulates the induction of necroptosis and apoptosis.A new level of regulation through its RIP homotypic interaction motif (RHIM) was recently discovered to suppress necroptosis and inflammation driven by the putative nucleic acid sensor protein Z-DNA binding protein 1 (ZBP1), also known as DAI.In the two decades following the discovery of RIPK1, RIPK1 has emerged as a master regulator of inflammatory signaling and cell death [1].To date, important advances in our understanding of RIPK1 function continue to be uncovered.RIPK1-deficient mice fail to thrive, die within 1-3 days following birth and display extensive apoptosis.These observations prompted initial research efforts to focus on the role of RIPK1 in controlling pro-survival and inflammatory gene expression.More recently, RIPK1 kinase activity emerged as essential for coordinating death receptor-