The review summarizes generalizing modern scientific data on the main functions of the protein HMGB1, and its physiological and pathological roles. Amphoterin is involved in key processes that ensure the functioning of DNA in the cell nucleus and plays an important role outside it. HMGB1 has been implicated in many human inflammatory diseases such as sepsis, ischemic reperfusion injury, neurological conditions, cardiovascular disease, autoimmune disease, and others. This manuscript describes the structure and main functions of HMGB1, discusses the significance of this alarmin as damage-associated molecular patterns, and analyzes its role in the development of inflammation and cell death. Special attention is focused on the role of HMGB1 in the development of endotoxemia, as well as data on the signaling pathways involved in its pathogenesis. Information on the results of studies of the possibility of modulating the activity of this protein using inhibitors is also considered, since understanding this may be useful for developing new therapeutic strategies aimed at treating inflammatory conditions of various origins.