{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nLY6E is an interferon‐inducible, glycosylphosphatidylinositol‐anchored cell surface protein that plays multifaceted roles in host–pathogen interactions and immune regulation. In the context of viral infection, LY6E enhances infectivity by promoting viral entry processes—including facilitating uncoating after endosomal escape and increasing membrane fusion—and its effects vary with cellular context. For example, LY6E can bolster HIV-1 infection by enhancing viral entry and gene expression in high-CD4–expressing cells, while in low-CD4 settings it downregulates CD4 levels to impede viral binding. In parallel, LY6E also acts as a negative regulator in monocytes by suppressing CD14 expression and attenuating LPS responses, and its increased expression correlates with disease activity in systemic lupus erythematosus."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the realm of oncology, aberrant LY6E expression has been identified in a broad spectrum of cancers—including breast, gastric, colorectal, lung, and ovarian malignancies—and is generally associated with poorer clinical outcomes. In breast cancer, for instance, LY6E promotes TGF-β signaling, facilitates phosphorylation of Smad molecules, and enhances the expression of immune checkpoint regulators such as PD-L1, thereby contributing to tumor proliferation, drug resistance, and immune evasion. Moreover, LY6E overexpression can activate pro-tumorigenic pathways through upregulation of HIF-1α via PTEN downregulation, which in turn increases angiogenic factors and tumor blood vessel density. In non-small cell lung cancer, LY6E interacts with nicotinic acetylcholine receptors to modulate TGF-β/Smad signaling, promoting epithelial–mesenchymal transition and cell migration. These oncogenic roles have spurred the development of therapeutic strategies such as antibody–drug conjugates targeting LY6E."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in viral pathology and tumor progression, LY6E has emerged as a candidate mediator in blood–brain barrier dynamics. Recent bioinformatic analyses and in vitro chip-based model studies have implicated LY6E in facilitating the transcytosis of adeno-associated virus particles across the human blood–brain barrier—thereby enhancing central nervous system gene delivery. This breadth of function underscores the potential utility of LY6E not only as a biomarker for diverse pathologies but also as a promising target for therapeutic intervention in infectious, oncological, and neurobiological diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Xuan Xu, Chao Qiu, Lingyan Zhu, et al. 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