Gbp6, a member of the guanylate-binding protein family, has been implicated in various biological processes. While its exact function in normal physiological conditions remains to be fully elucidated, it has been associated with immune-related pathways. In the evolutionary context, in muroid rodents, the Gbp6 gene shows a certain pattern of evolution, with an expansion in some species like Mus musculus and M. caroli, possibly to compensate for the loss of other Gbp genes [6].

In disease-related studies, in oral squamous cell carcinoma (OSCC), especially tongue squamous cell carcinoma (TSCC), Gbp6 is downregulated. Its low expression is correlated with poor cell differentiation, lymph node metastasis, and a poor disease-specific survival rate, suggesting it could serve as a diagnostic and prognostic biomarker [1]. In the tooth extraction model, Gbp6, along with Clec4e, is involved in inflammation and bone formation, and its knockdown increases osteogenic differentiation of mesenchymal stem cells [2]. In Mycobacterium avium subsp. paratuberculosis-infected cattle, Gbp6 is upregulated in subclinically infected animals, indicating its role in the immune response during the subclinical stage and its potential as a prognostic biomarker [3]. In the context of polymyositis with mitochondrial pathology (PM-Mito) and sporadic inclusion body myositis (IBM), GBP6 expression distinguishes IBM from PM-Mito, with IBM patients showing higher GBP6 expression, suggesting a role in type II IFN-induced inflammation [4]. In childhood tuberculosis, GBP6 is part of a sex-specific RNA biomarker signature for female pediatric patients, which could improve the diagnosis of TB disease [5]. In the study of nanoparticle-induced cytotoxicity in the retina, Gbp6 is involved in inflammatory-and apoptotic-related processes [7]. In the porcine familial adenomatous polyposis model, analysis of microdissected dysplastic epithelium showed possible new roles for GBP6 in adenoma progression [8].

In summary, Gbp6 is involved in multiple biological processes, especially those related to the immune response, inflammation, and disease progression. Its dysregulation is associated with various diseases such as oral cancers, tuberculosis, and myositis. Studies on Gbp6, including those using different research models, contribute to our understanding of disease mechanisms and the identification of potential biomarkers and therapeutic targets.