GBP4 is an interferon-γ-inducible GTPase that functions as a key component of innate immune defense against intracellular pathogens. Mechanistically, GBP4 assembles on the surface of cytosol-invading Gram-negative bacteria into polyvalent signaling platforms that recruit and activate caspase-4, leading to gasdermin-D-dependent pyroptosis and interleukin-18 processing 1. This bacterial destruction prevents intracellular replication and alerts neighboring cells to infection. Beyond its canonical antimicrobial role, GBP4 has emerged as a significant epigenetic driver in cancer. In intrahepatic cholangiocarcinoma, GBP4 demethylation correlates with aggressive phenotypes, regulating tumor proliferation, migration, and invasion 2. In pancreatic cancer, DNA hypomethylation-driven GBP4 upregulation paradoxically induces T cell exhaustion and immune checkpoint gene expression, yet tumors with high GBP4 show enhanced sensitivity to anti-PD-1 immunotherapy 3. Pan-cancer analysis confirms GBP4 as an inflammation marker that correlates with tumor-infiltrating immune cells and enhanced immunotherapy responsiveness 4. Clinically, GBP4 demonstrates diagnostic utility as a sex-specific RNA biomarker for pediatric tuberculosis 5 and shows diagnostic potential in EBV-associated gastric cancer 6. Promoter hypomethylation of GBP4 characterizes oral and oropharyngeal cancers 7, suggesting epigenetic dysregulation as a hallmark of malignant transformation.