Cathepsin E (EC: 3.4.23.34) (CTSE) is an intracellular gastric aspartyl protease. It was originally identified as a cathepsin D-like acid protease. It is active in acidic conditions in a pH range from 2.5 to 5.5. In vitro experiments have identified several CTSE substrates including insulin beta chain, neurokinin, and FGF. Although the function of CTSE is not completely understood, it has been implicated in several physiological and pathological processes. CTSE is required for antigen presentation on class II MHC molecules. CTSE-deficient macrophages show abnormalities such as autophagy. Like many other cathepsins, CTSE has emerged as a therapy target for cancers, such as pancreatic ductal adenocarcinoma (PDAC). In addition to PDAC, CTSE is