Abstract
The guanylate-binding protein (GBP) family, a group of interferon-induced GTPases, is pivotal in pathogen defense, inflammation regulation, and tumor immunity. Among them, GBP5 has emerged as a key player due to its distinctive roles in various diseases. However, existing studies reveal significant gaps, particularly regarding its expression, regulatory mechanisms, and functional dynamics across diverse diseases and patient populations, limiting its reliability as a biomarker or therapeutic target. This review provides a comprehensive synthesis of GBP5 functions across infectious diseases, cancer, immune disorders, and inflammation, with dedicated analysis of its context-dependent functional variability in distinct immune landscapes, genetic backgrounds, and disease progression stages. This systematic evaluation provides a critical foundation for future research, highlighting GBP5's promise as both a biomarker and therapeutic target in precision medicine.