{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nReelin is a large secreted glycoprotein that plays a critical role during brain development by orchestrating neuronal migration, positioning, and cortical lamination. Through binding to lipoprotein receptors such as very‐low–density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2), Reelin triggers intracellular cascades—including Disabled‐1 (Dab1) phosphorylation and downstream effectors like PI3‐kinase and protein kinase B—that are essential for proper dendritic development and synaptic modulation. In both human postmortem tissue and animal models, disruption of these signaling events has been shown to lead to marked laminar and positioning defects, underscoring Reelin’s indispensable role in constructing and fine tuning the cytoarchitecture of the central nervous system."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDysregulation of Reelin expression and function has been linked to a range of neuropsychiatric and neurodevelopmental disorders. Multiple studies have reported that abnormal Reelin promoter methylation, genetic variants (including polymorphic repeats), and altered messenger RNA/protein levels are associated with conditions such as autism spectrum disorder, schizophrenia, bipolar disorder, and epilepsy. In these disorders, decreased Reelin expression and improper processing can lead to faulty neuronal connectivity, impaired synaptic plasticity, and aberrant cortical organization—findings that have been observed in both clinical patient samples and relevant animal models."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "31"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its developmental functions, emerging evidence indicates that Reelin continues to influence the adult brain by modulating synaptic plasticity, dendritic spine density, and neurogenesis. Recent studies have also expanded its functional repertoire to include interactions with amyloid‐β species—delaying fibril formation and ameliorating neurotoxicity—as well as roles in receptor trafficking and extracellular proteolysis. 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