HMGB1 is present in the nuclei (chromatin associated) and cytoplasm of all cells and is a highly conserved protein in variety of species that. In the cytoplasm, HMGB1 is a regulator of autophagy, enhances cell survival, and limits apoptosis. It also can reduces protein aggregation caused by heat or chemical stress. HMGB1 is released to the extracellular milieu by inflammatory cells and by necrotic and apoptotic cells. Once released, it works as an inflammatory cytokine.HMGB1 is also secreted by macrophages and monocytes as a late response to LPS, TNF-α, IL-1β, or IFN-γ.