Because activation of the RAS/mitogen-activated protein kinase (MAPK) pathway contributes to the tumorigenesis and progression of ESCC and PITX1 has been identified as a negative regulator of the RAS pathway via the downregulation of RASAL1 [10], the epigenetic silencing of PITX1 may result in the activation of the RAS/MAPK pathway, leading to the hyperproliferation of the esophageal epithelium. The gene discussed is WNK2; the disease is esophageal squamous cell carcinoma.