REVIEW article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1708319
From mechanisms to therapies: the multifaceted roles of guanylate-binding protein 2 in immunity, cancer, and beyond
Provisionally accepted
- 1Sheng Jing Hospital Affiliated, China Medical University, Shenyang, China
- 2First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
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Guanylate-binding protein 2 (GBP2) is an interferon-inducible GTPase that plays a critical role in innate immunity by defending against viral, bacterial, and parasitic infections through mechanisms such as furin inhibition and inflammasome activation. Beyond infectious disease, GBP2 demonstrates a context-dependent dual role in cancer—acting as either a tumor suppressor or an oncogene by modulating key signaling pathways including JAK-STAT, Wnt/β-catenin, and PI3K/AKT/mTOR. Its dysregulation is also increasingly implicated in autoimmune, neurological, and metabolic disorders, underscoring its promising utility as a diagnostic biomarker and therapeutic target. This review systematically synthesizes current knowledge on GBP2's structural features, biological functions, and functional duality. We further explore the paradoxical nature of its context-dependent roles and propose a unifying hypothesis to explain its dual functions, while outlining translational strategies to leverage GBP2's potential in biomarker development and targeted therapies.
Keywords: guanylate-binding protein 2 (GBP2), interferon-inducible GTPase, innate immunity, Inflammasome, Cancer, biomarker, Therapeutic target
Received: 18 Sep 2025; Accepted: 02 Oct 2025.
Copyright: © 2025 Cui, Wang and Feng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Juan Feng, juanfeng@cmu.edu.cn
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