Intracellular and secreted CTSD requires a low pH to exert its proteolytic activity, leading to the speculation that CTSD activity may be especially enhanced in the acidic environment of gastroesophageal reflux associated disease.20,27 CTSD is also involved in the resistance to the bile salt deoxycholate–induced apoptosis in colon cancer cell lines.28 Because CTSE is highly homologous to CTSD, there may be a similar acid and bile-associated function for CTSE in the context of BE development.9,26. This evidence concerns the gene CTSE and malignant colon neoplasm.