As an evolutionarily conserved DNA-binding protein presenting with high electrophoretic mobility, HMGB1 was abundantly found in the nucleus and initially known to play essential roles in maintaining genome homeostasis and cell survival.164,165 During sterile injuries and infections, extracellular HMGB1 is able to alert innate immune response and regulate inflammation by acting as an endogenous prototypical DAMP.166 Later, HMGB1 is proven as a late-phase inflammatory mediator that drives endotoxin lethality in sepsis. The gene discussed is HMGB1; the disease is Sepsis.