{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cathepsin V (CTSV) is a human‐specific lysosomal cysteine protease that performs a variety of functions in both normal physiology and disease. In the thymus, CTSV is highly expressed in cortical epithelial cells where it mediates the proteolytic processing of the invariant chain into CLIP, a critical step in MHC class II antigen presentation (1). In peripheral tissues, CTSV is a potent elastase whose unique exosites enable efficient degradation of elastin and extracellular matrix proteins, a function that contributes to the weakening of arterial walls in atherosclerosis and the loss of skin elasticity with aging (2,3). In the epidermis, CTSV participates in keratinocyte differentiation by processing substrates such as transglutaminase 3, and its activity is tightly controlled by inhibitors like cystatin M/E; this regulation is essential for maintaining proper skin barrier formation and hair follicle integrity (4,5). Post‐translational modifications, notably N‐glycosylation at specific asparagine residues, are critical for its intracellular trafficking to lysosomes, secretion, and proteolytic activity (6). Moreover, CTSV has been implicated in noncanonical roles such as the processing of neuropeptide precursors—generating active enkephalin and neuropeptide Y to facilitate neurotransmission in the brain (7)—and, when mislocalized to the nucleus in thyroid epithelial and carcinoma cells, it appears to promote cell cycle progression and hyperproliferation (8). In addition, altered CTSV expression is observed in pathological conditions; for example, reduced levels in the skin and serum are associated with fibrotic and vasculopathic changes in systemic sclerosis (9), while in cancers such as endometrial and breast carcinoma, elevated CTSV drives tumor progression by modulating the degradation of key regulatory proteins like GATA3 (10). Collectively, these findings underscore the multifaceted roles of CTSV in antigen processing, extracellular matrix remodeling, epithelial differentiation, neuropeptide formation, and the modulation of tumor cell behavior.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n (1)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "; (2)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "; (3)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "; (4)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "; (5)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "; (6)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "; (7)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "; (8)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "; (9)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "; (10)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Eva Tolosa, Weijie Li, Yoshiyuki Yasuda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cathepsin V is involved in the degradation of invariant chain in human thymus and is overexpressed in myasthenia gravis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI18028"}], "href": "https://doi.org/10.1172/JCI18028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12925692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12925692"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yoshiyuki Yasuda, Zhenqiang Li, Doron Greenbaum, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cathepsin V, a novel and potent elastolytic activity expressed in activated macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M403986200"}], "href": "https://doi.org/10.1074/jbc.M403986200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15192101"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15192101"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xin Du, Nelson L H Chen, Andre Wong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elastin degradation by cathepsin V requires two exosites."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.510008"}], "href": "https://doi.org/10.1074/jbc.M113.510008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24121514"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24121514"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tsing Cheng, Kiyotaka Hitomi, Ivonne M J J van Vlijmen-Willems, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cystatin M/E is a high affinity inhibitor of cathepsin V and cathepsin L by a reactive site that is distinct from the legumain-binding site. A novel clue for the role of cystatin M/E in epidermal cornification."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M600694200"}], "href": "https://doi.org/10.1074/jbc.M600694200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16565075"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16565075"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sascha Hagemann, Thomas Günther, Julia Dennemärker, et al. 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