At present, a growing body of both basic and clinical pieces of evidence supports the crucial contribution of the RAGE axis to several pathological settings, such as cardiovascular disease, neurodegeneration, metabolic diseases, and immune/inflammatory diseases as well as several types of cancer [2,3,4], mainly through its capacity to function as an efficient hub to evoke a potent and sustained inflammatory response triggered by different stimuli (Figure 2). This evidence concerns the gene AGER and metabolic disease.