{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSERPINF1 encodes pigment epithelium‐derived factor (PEDF), a secreted glycoprotein belonging to the serpin family that has emerged as a multifunctional regulator in diverse tissues. PEDF is one of the most potent endogenous inhibitors of angiogenesis and plays key neurotrophic and anti‐inflammatory roles. Its biochemical activity is modulated via specific interactions with extracellular matrix components—such as collagens and heparan sulfate proteoglycans—which help localize its activity and fine‐tune its antiangiogenic effects in the eye and vasculature. In various ocular models, PEDF counteracts proangiogenic mediators like VEGF, reduces oxidative stress, and protects the blood–retinal barrier, thereby limiting vascular permeability and inflammation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its vascular and neuroprotective activities, PEDF is critically involved in bone homeostasis. Loss‐of‐function mutations in SERPINF1 have been causally linked to osteogenesis imperfecta type VI—a distinct form of inherited bone fragility in which patients display severe fractures, long‐bone deformities, and excess unmineralized osteoid despite normal collagen synthesis. Beyond the skeletal system, PEDF modulates metabolic processes by influencing insulin sensitivity and adipocyte function, and it can attenuate inflammatory responses via suppression of oxidative stress (for example, by down‐regulating NADPH oxidase subunit expression). These findings underscore the importance of PEDF in maintaining both skeletal integrity and systemic metabolic balance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "34"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, PEDF exerts potent antitumorigenic and tissue‐protective effects in multiple contexts. In various cancer models—including hepatocellular, pancreatic, prostate, and osteogenic malignancies—PEDF suppresses tumor growth, invasion, and angiogenesis by interfering with proangiogenic signaling and inflammatory mediators such as interleukin‑8. Its receptor‐mediated signaling cascades have been linked to the inhibition of NADPH oxidase activity and reduction of reactive oxygen species, thereby promoting cell survival and reducing endothelial activation. In ocular and corneal models, PEDF supports neuroprotection, promotes limbal stem cell expansion, and facilitates wound healing. The convergence of these signaling pathways and receptor interactions not only highlights PEDF’s diverse biological roles but also positions SERPINF1 as a promising therapeutic target in ocular diseases, cancer, and metabolic disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "35", "end_ref": "48"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jutta Becker, Oliver Semler, Christian Gilissen, et al. 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