GBP3 is an interferon-γ-inducible GTPase that functions as a critical component of intracellular innate immunity, with context-dependent roles in both antimicrobial defense and pathological inflammation. In antimicrobial responses, GBP3 governs caspase-4 activation on cytosolic bacterial surfaces by assembling polyvalent signaling platforms with other GBPs, ultimately triggering gasdermin-D-dependent pyroptosis and interleukin-18 processing to eliminate intracellular bacteria 1. GBP3 directly binds lipopolysaccharide of Gram-negative bacteria and localizes to intracellular microbes through membrane binding and protein trafficking 2. Beyond antimicrobial immunity, GBP3 participates in cancer-associated pathways. In glioblastoma, GBP3 promotes cell proliferation via the SQSTM1/p62-ERK1/2 axis 3 and enhances chemotherapy resistance by stabilizing STING protein, which upregulates DNA damage repair pathways including NRF2 and MGMT expression 4. Pan-cancer analyses reveal context-dependent prognostic significance, with elevated GBP3 associated with increased mortality in brain glioma and lung squamous cell carcinoma but decreased risk in melanoma 5. Additionally, GBP3 participates in a STAT1-GBP3-STING feedback loop driving aortic inflammation and oxidative stress in acute aortic dissection 6. GBP3 expression is restricted to Simiiformes, likely originating from GBP1 gene duplication during primate evolution 7.