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, AGER is linked to cancer.