{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nOSBP2, also known as ORP4, belongs to a family of lipid‐binding proteins that recognize and transfer sterols, oxysterols, and phosphoinositides between membranes. Its conserved oxysterol‐binding domain mediates not only the extraction and transport of these lipids but also contributes to the organization of intracellular structures. For example, ORP4 interacts with filamentous vimentin to influence cytoskeletal integrity and, in an oxysterol‐ and PI(4)P-dependent manner, helps maintain the architecture and phosphoinositide content of the Golgi and trans‐Golgi network. In addition, the binding of potentially cytotoxic oxysterols in specialized cells—including retinal pigment epithelium—underscores its broader role in mitigating lipid‐induced stress."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, the ORP4 isoforms—most notably ORP4L—are critical regulators of cell proliferation and survival. They help maintain intracellular Ca²⁺ homeostasis by sustaining endoplasmic reticulum Ca²⁺ stores and supporting the expression of key Ca²⁺ channels such as the IP₃ receptor. Acting as a molecular scaffold, ORP4L couples components of G protein–coupled receptor signaling (including CD3ε, Gαq/11 and distinct phospholipase C isoforms) to promote IP₃-induced Ca²⁺ release, NFAT activation, and downstream transcriptional events that drive cellular growth. In T-cell acute lymphoblastic leukemia, for instance, elevated ORP4L expression enhances mitochondrial ATP production and survival signaling. Additionally, ORP4L’s ability to interact directly with the IP₃ receptor type 1 further amplifies its role in regulating Ca²⁺ dynamics and oncogenic pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, aberrant expression and genetic variations in OSBP2/ORP4 have been linked to a range of pathologies. Elevated levels or specific allelic variants correlate with aggressive behavior in several cancers—including solid tumors, cholangiocarcinoma, hepatocellular carcinoma, and T-cell leukemias—and may serve as biomarkers for disease progression and metastasis. In some contexts, such as chronic myeloid leukemia and adult T-cell leukemia, OSBP2 expression is associated with the maintenance of undifferentiated states and oncogenic signaling (for example, via enhanced PI3K/AKT pathway activity). Similarly, OSBP2 has been implicated in host–virus interactions by negatively regulating hepatitis C virus replication through its association with viral replicase components, suggesting its potential as a therapeutic target."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jessica P Wyles, Ryan J Perry, Neale D Ridgway "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of the sterol-binding domain of oxysterol-binding protein (OSBP)-related protein 4 reveals a novel role in vimentin organization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2007.01.018"}], "href": "https://doi.org/10.1016/j.yexcr.2007.01.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17350617"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17350617"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Margherita Torrini, Cristiana Marchese, Mario Vanzetti, et al. 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