Abnormal extracellular HMGB1 might contribute to the pathophysiology of epilepsy-related hyperexcitability as evidenced by study on PRNCs demonstrate a surge in extracellular HMGB1 approximated seizure initiation, establishing HMGB1 as a key pathophysiological contributor to the onset of epilepsy-related hyperexcitability (Table 3) (Kaneko et al., 2017). This evidence concerns the gene HMGB1 and epilepsy.