Extracellular HMGB1 can interact with TLR4 or RAGE, initiating signal transduction cascades that activate NF-κB, consequently facilitating the production of pro-inflammatory cytokines and contributing to various pathological conditions, including sterile inflammation (54), autoimmune disorders (55), septic shock (56), cancer (50), and AKI (57). Here, HMGB1 is linked to acute kidney injury.