The debate regarding the source and role of BE continues unabated, and recently, an exhaustive and thorough study using transcriptomics and genomic techniques concluded that the MB arises from undifferentiated gastric cardia via cMYC and HNF4A transcriptional pathways and that EAC arises from undifferentiated Barrett’s cell types with no identifiable precursor [21]. The gene discussed is HNF4A; the disease is Barrett esophagus.