CTSD and gastroesophageal reflux disease: Interestingly, the other cathepsin family members cathepsin B, C, K, and S are also up-regulated in BE and EAC, and cathepsin D (CTSD) mRNA expression shows a significant stepwise increase in erosive esophagitis, intestinal metaplasia and EAC.17–20 Further functional hypotheses for CTSE in Barrett disease involve the contents of the gastro-esophageal refluxate.