High-mobility group protein B1 (HMGB1) is also known as high-mobility group protein 1 (HMG-1) and amphoterin, is a member of the HMGB family consisting of three members, HMGB1, HMGB2 and HMGB3. HMGB1 is a non-histone architectural chromosomal protein ubiquitously present in all vertebrate nuclei and binds double-stranded DNA without sequence specificity. The mechanism of inflammation and damage is binding to TLR4, which mediates HMGB1-dependent activation of macrophage cytokine release. This positions HMGB1 at the intersection of sterile and infectious inflammatory responses. HMGB1 has been studied as a DNA vaccine adjuvant and a target for cancer therapy.