{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cathepsin E (CTSE) is an endolysosomal aspartic protease predominantly expressed by cells of the immune system that plays multifaceted roles in health and disease. In antigen‐presenting cells such as microglia and dendritic cells, CTSE contributes to the proteolytic cleavage of native proteins to release antigenic epitopes for presentation via major histocompatibility complex class II molecules."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In addition, CTSE is implicated in regulating lysosomal homeostasis; its deficiency can lead to the accumulation of lysosomal membrane proteins (e.g., LAMP‐1 and LAMP‐2) and an elevated lysosomal pH in macrophages, phenomena that in turn affect antigen processing and innate immune functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond these immunologic roles, CTSE has been shown to mediate antitumor functions. In human prostate carcinoma cell lines, for example, CTSE catalyzes the proteolytic release of soluble, apoptosis‐inducing ligands (TRAIL), thereby promoting growth arrest and apoptosis, which underscores its potential role in tumor suppression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Conversely, in CTSE‐deficient mice, dysregulated cytokine turnover—with slower degradation of proinflammatory cytokines such as interleukin‐18 and IL‐1β—can contribute to inflammatory disorders including atopic dermatitis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n CTSE has also attracted attention as a molecular imaging target. Its markedly elevated expression in pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma has been exploited to develop activity‐based fluorescent probes for early in vivo tumor detection."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In the skin, a CTSE‐like proteolytic activity has been identified as participating in desquamation, in part via the hydrolysis of corneodesmosin—a key protein for cell–cell adhesion in the stratum corneum."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, CTSE expression is subject to transcriptional regulation; for instance, the MHC class II transactivator (CIITA) can negatively regulate CTSE expression in antigen‐presenting cells, thereby fine‐tuning the repertoire of peptides generated for immune surveillance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, studies in distinct antigen‐presenting cell subsets reveal that CTSE deficiency can differentially affect phagocytic degradation and subsequent T‐cell activation, highlighting its role in tailoring immune responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Structural analyses further distinguish CTSE from other aspartic proteases (such as cathepsin D and BACE1), with subtle active‐site differences that may be exploited for the development of selective inhibitors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Moreover, CTSE has been implicated in host defense against bacterial pathogens by modulating endosome‐associated processing activities."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings establish CTSE as an important mediator in antigen processing, immune regulation, tissue homeostasis, and tumor suppression. Its diverse functions and disease‐associated dysregulation underscore its potential as both a diagnostic biomarker and a selective therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tsuyoshi Nishioku, Koichi Hashimoto, Keizo Yamashita, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of cathepsin E in exogenous antigen processing in primary cultured murine microglia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M108382200"}], "href": "https://doi.org/10.1074/jbc.M108382200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11719510"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11719510"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Benjamin M Chain, Paul Free, Patrick Medd, et al. 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