The RAGE axis is a pattern recognition receptor (PRR) that recognizes a wide range of ligands, including advanced glycation end-products (AGEs) and alarmins, and plays a crucial role in various human diseases. RAGE is expressed in multiple tissues, with high levels in the lungs and alveolar epithelial cells. Its activation triggers signaling pathways that lead to inflammation, oxidative stress, and tissue damage, contributing to diseases such as diabetes, neurodegenerative disorders, cardiovascular diseases, autoimmune conditions, chronic airway diseases, and cancer. RAGE ligands include AGEs, HMGB1, S100 proteins, and others, and their interaction with RAGE leads to the activation of pro-inflammatory and fibrotic responses. The RAGE axis is also involved in the progression of diseases like diabetic retinopathy, nephropathy, and atherosclerosis, as well as in the development of cancer through mechanisms such as tumor hypoxia, immune suppression, and genomic instability. The RAGE axis is a key mediator of inflammation and tissue damage in many diseases, and its modulation could offer therapeutic potential. However, the role of RAGE in disease pathogenesis is complex, and its ligands and signaling pathways are still being studied. The RAGE axis is also associated with genetic variations that may influence disease susceptibility and progression. Overall, the RAGE axis is a critical inflammatory hub in human diseases, and understanding its biology and signaling pathways is essential for developing targeted therapies.The RAGE axis is a pattern recognition receptor (PRR) that recognizes a wide range of ligands, including advanced glycation end-products (AGEs) and alarmins, and plays a crucial role in various human diseases. RAGE is expressed in multiple tissues, with high levels in the lungs and alveolar epithelial cells. Its activation triggers signaling pathways that lead to inflammation, oxidative stress, and tissue damage, contributing to diseases such as diabetes, neurodegenerative disorders, cardiovascular diseases, autoimmune conditions, chronic airway diseases, and cancer. RAGE ligands include AGEs, HMGB1, S100 proteins, and others, and their interaction with RAGE leads to the activation of pro-inflammatory and fibrotic responses. The RAGE axis is also involved in the progression of diseases like diabetic retinopathy, nephropathy, and atherosclerosis, as well as in the development of cancer through mechanisms such as tumor hypoxia, immune suppression, and genomic instability. The RAGE axis is a key mediator of inflammation and tissue damage in many diseases, and its modulation could offer therapeutic potential. However, the role of RAGE in disease pathogenesis is complex, and its ligands and signaling pathways are still being studied. The RAGE axis is also associated with genetic variations that may influence disease susceptibility and progression. Overall, the RAGE axis is a critical inflammatory hub in human diseases, and understanding its biology and signaling pathways is essential for developing targeted therapies.