Gbp5, short for Guanylate-binding protein 5, belongs to the GTPase subfamily and is mainly induced by interferon gamma (IFN-γ). It is involved in multiple cellular processes, such as inflammasome activation, innate immunity, and regulation of cellular inflammatory responses [6]. It has been associated with various signaling pathways, including NF-κB, NLRP3 inflammasome-related, and Src/ERK1/2/MMP3 pathways [1,2,3,5].

In rosacea-like skin inflammation, macrophage depletion ameliorated the condition, and Gbp5 was identified as a hub gene associated with macrophage infiltration. Silencing Gbp5 attenuated the inflammation by suppressing M1 macrophage polarization via the NF-κB pathway [1].

In osteoarthritis, Gbp5 expression increased in TNF-α-induced chondrocytes and in the cartilage of OA mice and human patients. Gbp5 knockout reduced chondrocyte injury, as it promotes chondrocyte pyroptosis through the NLRP3 inflammasome signaling pathway [2].

In collagen-induced arthritis, sinomenine binds to Gbp5, downregulates P2X7R, and suppresses NLRP3-related pathways [3].

In liver injury, Gbp5 knockout ameliorated D-galactosamine/lipopolysaccharide-induced injury, as Gbp5 promotes hepatocyte apoptosis through calpain/caspase and TNFα/caspase pathways [4].

In glioblastoma, silencing Gbp5 impaired tumor growth, as Gbp5 promotes malignancy via the Src/ERK1/2/MMP3 pathway [5].

In lupus nephritis, Gbp5 inhibition suppressed NLRP3 inflammasome activation and prevented disease progression [7].

In triple-negative breast cancer, Gbp5 knockdown suppressed metastatic potential and PD-L1 expression [8].

In conclusion, Gbp5 plays significant roles in inflammation, cell death, and tumor-related processes. Gene knockout models in mice have been crucial in revealing its functions in diseases such as rosacea, osteoarthritis, arthritis, liver injury, glioblastoma, lupus nephritis, and triple-negative breast cancer, providing potential therapeutic targets for these conditions.