{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Lacritin is a secreted glycoprotein predominantly produced by the lacrimal and accessory lacrimal glands that plays a central role in maintaining ocular surface homeostasis. Multiple studies demonstrate that lacritin acts as an autocrine/paracrine prosecretory mitogen, stimulating basal tear protein secretion and promoting epithelial cell proliferation and wound healing through activation of signaling pathways—including protein kinase C, calcium‐mediated, NFAT, and mTOR pathways (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "]). Its bioactivity is largely mediated by a conserved C‐terminal amphipathic α–helical domain that, following proteolytic processing, confers both mitogenic and antimicrobial properties as well as the ability to stabilize the tear lipid layer (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "]). Furthermore, lacritin engages cell surface syndecan‐1 through its C-terminal domain after enzymatic removal of glycosaminoglycan chains by heparanase, a key step for its receptor binding and subsequent signaling (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "]). Alterations in lacritin’s expression, glycosylation, and enzymatic cross–linking have been observed in a spectrum of ocular surface diseases—including blepharitis, various forms of dry eye, keratitis, and Graves’ orbitopathy—making it both a potential biomarker and therapeutic target in these disorders (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "], ["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "]). Topical application of recombinant lacritin not only restores basal tear secretion with sustained efficacy but also enhances epithelial cytoprotection, underscoring its therapeutic promise (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "]). In addition to its established role in the eye, lacritin transcripts have been detected in extraglandular tissues such as the breast, suggesting that its homeostatic and mitogenic functions may extend beyond the ocular surface (["}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "]).\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "S Sanghi, R Kumar, A Lumsden, et al. 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