Fgl2, a member of the thrombospondin family and fibrinogen-related proteins family, is a multifunctional protein. It is known for modulating prothrombin activity, inducing immune tolerance, and regulating the activity of immune cells and tumor cells. It is involved in various pathways such as those related to coagulation, inflammation, and immune-regulation, which are crucial in many biological processes and disease conditions [1,2,4]. Genetic models like gene knockout (KO) mouse models are valuable for studying its functions.

In melanoma and ovarian cancer models, Fgl2 knockout mice demonstrated that absence of Fgl2 led to a more activated tumor microenvironment (TME), with activated dendritic cells, T cells, and natural killer cells, and prolonged survival in the B16F10 melanoma model, and synergized with oncolytic virus in the ID8-p53-/-Brca2-/-ovarian cancer model, indicating Fgl2 promotes tumour growth and attenuates infiltration of activated immune cells [5]. In glioblastoma, T cells expressing Fgl2-specific single-chain variable fragments can induce tumor-specific CD8+ tissue-resident memory T (TRM) cells that prevent glioblastoma recurrence, suggesting a role in anti-glioblastoma immunity [3]. Also, Fgl2 deficiency alleviated maternal inflammation-induced blood-brain barrier damage by blocking PI3K/NF-κB mediated endothelial oxidative stress in a mouse model of maternal inflammation [6].

In conclusion, Fgl2 is crucial in regulating immune responses, tumour growth, and inflammation-related processes. KO mouse models have been instrumental in revealing its role in cancer, such as melanoma, ovarian cancer, and glioblastoma, as well as in conditions like maternal-inflammation-induced brain damage. Understanding Fgl2's functions provides potential therapeutic targets for these diseases.