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High-mobility group protein B1 （HMGB1）, also referred to as high-mobility group protein 1 （HMG-1） or amphoterin, is a member of the HMGB family, which includes HMGB1, HMGB2, and HMGB3. HMGB1 is a non-histone architectural chromosomal protein found in all vertebrate nuclei and binds double-stranded DNA without sequence specificity. It plays a role in the mechanisms of inflammation and damage by binding to TLR4, thereby mediating HMGB1-dependent activation of macrophage cytokine release. This places HMGB1 at the crossroads of sterile and infectious inflammatory responses. Studies have explored HMGB1 as an adjuvant for DNA vaccines and as a potential target for cancer therapy.