AGER (advanced glycosylation end-product specific receptor) is a cell surface pattern recognition receptor that functions as a multiligand sensor for endogenous damage signals 12345. Upon ligand binding—including advanced glycation end products (AGEs), S100 proteins, HMGB1, amyloid-beta, and nucleic acids—AGER transduces pro-inflammatory responses via TIRAP/MYD88 adapters, activating NF-κB and inducing inflammatory cytokines 67. AGEs accumulate in vascular tissue during aging and diabetes, accelerating pathogenic processes 8. Mechanistically, AGER mediates diverse cellular responses: it promotes HMGB1-driven inflammation in ferroptosis through a RAGE-dependent but TLR4-independent pathway 9, facilitates macropinocytosis in KRAS-G12D pancreatic cancer cells to enable drug resistance via interaction with DIAPH1 10, and participates in AGE-mediated extracellular matrix remodeling that promotes hepatocellular carcinoma progression 11. AGER also drives S100A9-dependent skeletal muscle wasting through the PGAM5-BNIP3 mitophagy axis 12. Clinically, AGER dysfunction associates with idiopathic pulmonary fibrosis susceptibility; the rs2070600 polymorphism increases disease risk and reduces soluble RAGE levels, predicting poor survival 13. Additionally, AGER mediates epithelial pathogenesis in COPD through IL-33ox-dependent signaling 14. These findings identify AGER as a therapeutic target across inflammatory, fibrotic, and malignant diseases.