{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Human tissue kallikrein‐14 (KLK14) is a secreted serine protease with trypsin‐like activity that plays multifaceted roles in both normal physiology and disease. KLK14 participates in epidermal desquamation by cleaving key components of the corneodesmosomes such as desmoglein‐1, thereby contributing to the shedding of the stratum corneum particularly in specialized regions like the plantar skin, where despite its low abundance the active enzyme accounts for a substantial portion of trypsin‐like proteolytic activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Its activity is tightly regulated by several endogenous inhibitors: diverse LEKTI fragments have been shown to potently inhibit KLK14"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "and in concert with other inhibitors such as SPINK6, contribute to the precise modulation needed for proper desquamation and barrier homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in skin differentiation, KLK14 can engage in extracellular signaling; it is capable of activating protease‐activated receptor‐2 (PAR2) on keratinocytes, a process that may amplify local inflammatory responses in conditions associated with barrier dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " From a biochemical perspective, KLK14 exhibits a dual enzymatic profile – demonstrating both trypsin‐ and chymotrypsin‐like activities with high selectivity for cleaving after arginine residues – a property that is modulated via autoactivation and autolytic inactivation, as well as inhibition by several serine protease inhibitors"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "and further detailed through substrate profiling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, emerging evidence has linked elevated expression and activity of KLK14 with tumor progression, where its ability to degrade extracellular matrix components such as collagens, fibronectin, and laminin could facilitate growth, invasion, and angiogenesis in various cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, KLK14 is a key protease whose regulated activity is essential for normal epidermal turnover and barrier maintenance, while its dysregulation may contribute to inflammatory skin disorders and tumor progression. These multifaceted roles make KLK14 a promising candidate for targeted diagnostic and therapeutic strategies across both dermatological and oncological disease settings."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kristina Stefansson, Maria Brattsand, Annelii Ny, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kallikrein-related peptidase 14 may be a major contributor to trypsin-like proteolytic activity in human stratum corneum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1515/BC.2006.095"}], "href": "https://doi.org/10.1515/BC.2006.095"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16800737"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16800737"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Celine Deraison, Chrystelle Bonnart, Frederic Lopez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e07-02-0124"}], "href": "https://doi.org/10.1091/mbc.e07-02-0124"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17596512"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17596512"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ulf Meyer-Hoffert, Zhihong Wu, Tomasz Kantyka, et al. 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