The extracellular S100A14 was shown to bind with RAGE leading to the activation of mitogen activated protein (MAP) kinase (extracellular signal-regulated kinase, ERK) and NF-κB signaling pathways, thereby promoting cell proliferation and survival in esophageal squamous cell carcinoma (ESCC) (Figure 2). The gene discussed is S100A14; the disease is esophageal squamous cell carcinoma.