High-mobility group protein B1 (HMGB1) is a protein consisting of 215 amino acid residues which is coded by the HMGB1 gene on chromosome 13q12.3. High-Mobility Group (HMG) chromosomal proteins are the most significant nuclear non-histone proteins in humans. As all other members of the non-histone chromosomal high-mobility group protein family, HMGB1 is a chromatin-associated protein which is ubiquitously distributed in human cells. HMGB1 is the second most abundant protein (after histone) inside the nucleus. It exerts multiple functions in the nucleus, the cytoplasm, and in the extracellular space. In the nucleus, HMGB1 plays a role in the maintenance of nucleosome structure, as well as the regulation of DNA replication, transcription, and repair. HMGB1 increases the binding affinity of many transcription factors (for example: p53, Rb, NF-κB, estrogen receptor) to their target DNA sequences. Probably due to its ability to specifically bind to damaged DNA sequences, HMGB1 contributes to the early stage of DNA repair. In the extracellular space, HMGB1 acts as a damage-associated molecular pattern molecule (DAMP) that mediates inflammation and immune responses. In case of tissue damage, HMGB1 is released through active secretion of HMGB1 from monocytes, natural killer cells, dendritic cells (DC), platelets, and endothelial cells or by passive release from the nuclei of necrotic cells. Extracellular HMGB1 is thought to contribute to various conditions, including sepsis, atherosclerosis, arthritis, neurodegeneration, meningitis, and cancer. Therapeutic options to regulate HMGB1 in preclinical models are being evaluated.    Suggested reading: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104204/