Identified in 1999 as a late-stage mediator of sepsis, HMGB1 acts as a damage-associated molecular pattern (DAMP), prolonging inflammation by activating macrophages via Toll-like receptor 4 (TLR4) and the receptor for Advanced Glycation Endproduct (RAGE) pathways [49,50,51,52]. The gene discussed is HMGB1; the disease is Sepsis.