SHARPIN and systemic inflammatory response syndrome: Necroptosis is emerging as an important form of cell death involved in a wide variety of inflammatory or degenerative disorders including tumor necrosis factor (TNF)-induced systemic inflammatory response syndrome (SIRS)11,12, systemic inflammatory responses in A20−/− mice13,14, chronic proliferative dermatitis (cpdm) in SHARPIN−/− mice12, colitis15, neurodegenerative diseases16 and ischemia–reperfusion-induced injury in the brain17, kidney18,19, and heart20,21.