Flipping the Switch from Inflammation to Cell Death

Multiple research groups have demonstrated that caspase-8 (CASP8)-mediated gasdermin D (GSDMD) cleavage drives pyroptotic cell death. Here, we discuss a novel role for the enzymatically inactive homolog of CASP8, the long isoform of cellular FLICE-like inhibitory protein (cFLIP(L)), in the regulation of this process. Specifically, cFLIP-deficiency provides a model in which to study the mechanisms regulating CASP8-mediated activation of cell death and inflammatory signaling.