High-mobility group box 1 protein (HMGB1), also known as HMG-1 or amphoterin previously, is a member of the HMGB family consisting of three members, HMGB1, HMGB2 and HMGB3. Posttranslational modification of HMGB1, including acetylation, phosphorylation, and methylation, affects HMGB1 localization, receptor interactions, and bioactivity. HMGB1 can be localized to the nucleus or cytoplasm and can also be secreted despite its lack of a signal peptide. HMGB1 binds DNA in a non-sequence specific manner and may act as a structural cofactor during gene transcription.Acetylation of HMGB1 results in its cytoplasmic localization and eventual secretion. HMGB1 can be secreted by multiple cell types, and it is also released upon cell necrosis, apoptosis, and pyroptosis.