Recent studies have identified necroptosis mediated by the Z-DNA-binding protein 1 (ZBP1) - receptor interaction protein kinase 3 (RIPK3) - mixed lineage kinase-like protein (MLKL) signaling pathway and pyroptosis mediated by the cysteine-aspartic acid proteases-11 (caspase-11) - Gasdermin D (GSDMD) pathway as key mechanisms in heat stroke and sepsis, respectively. The gene discussed is ZBP1; the disease is Sepsis.