GBP3 is an interferon-inducible guanylate-binding protein that serves antimicrobial and immunoregulatory functions. The protein shows prominent antiviral activity in epithelial cells and functions as a GTPase that localizes to the cytoplasm and cytosolic vesicles. In the canonical innate immune pathway, GBP3 assembles on the surface of cytosol-invading Gram-negative bacteria into signaling platforms that activate caspase-4, triggering gasdermin-D-dependent pyroptosis and interleukin-18 processing to eliminate intracellular pathogens 1. GBP3 can directly bind bacterial lipopolysaccharides and participates in pathogen sensing and host defense 2. Beyond infection control, GBP3 participates in inflammation and oxidative stress responses; recent evidence suggests a STAT1-GBP3-STING positive feedback loop governs these processes and aortic remodeling in acute aortic dissection 3. GBP3 expression is dysregulated in multiple cancers with context-dependent effects: elevated expression associates with increased risk in brain lower-grade glioma and lung squamous cell carcinoma but decreased risk in sarcoma and skin melanoma 4. In glioblastoma specifically, GBP3 promotes cell proliferation via the SQSTM1-ERK1/2 axis and confers resistance to temozolomide chemotherapy by enhancing DNA damage repair through STING-mediated pathways 56. GBP3 reduction sensitizes glioblastoma cells to temozolomide in preclinical models, suggesting therapeutic potential for targeting this protein in drug-resistant tumors.