GBP6 is an interferon-inducible GTPase that functions as a key component of innate immunity against diverse pathogens. As a member of the guanylate-binding protein family, GBP6 exhibits GTPase activity and GTP binding capability, localizing to cytoplasmic compartments and extracellular exosomes 1. The protein plays critical roles in defense responses to bacterial pathogens and protozoan infections, with recent evidence demonstrating its involvement in trained immunity following mycobacterial infection, where infection-induced epigenetic changes at the Gbp6 locus are conserved from hematopoietic stem cells to differentiated monocytes 2. Clinically, GBP6 serves as a robust diagnostic and prognostic biomarker across multiple disease contexts. In tuberculosis, GBP6 expression distinguishes active pulmonary TB from other respiratory diseases and latent TB infection from healthy controls 3, with sex-specific GBP6 signatures showing 85% sensitivity and 70% specificity in pediatric TB diagnosis 4. GBP6 is significantly upregulated in inclusion body myositis compared to polymyositis with mitochondrial pathology, marking type II interferon-induced inflammation 1. Paradoxically, GBP6 shows tumor-suppressive functions in epithelial malignancies. Low GBP6 expression correlates with poor prognosis in tongue squamous cell carcinoma and esophageal carcinoma, with loss of GBP6 promoting epithelial-mesenchymal transition and cell cycle acceleration 5 6 7. These findings position GBP6 as a multifunctional immune-oncology biomarker with distinct roles in pathogen defense and cancer progression.