Ffar2, also known as GPR43, is a G-protein-coupled receptor activated by short-chain fatty acids (SCFAs) such as acetate, butyrate, and propionate. It plays a crucial role in linking metabolism and immunity. Through multiple signaling pathways like AKT, ERK, and the AKT-STAT3 axis, it participates in regulating various biological processes [4,6]. It is important for gut homeostasis, host defense, and immune responses [1]. Genetic models, especially knockout mouse models, have been instrumental in studying its functions.

In gene knockout studies, Ffar2 deficiency in ILC3s led to decreased in-situ proliferation and interleukin-22 production, impairing gut epithelial function and increasing susceptibility to colonic injury and bacterial infection [1]. In myeloid-derived suppressor cells (MDSCs), whole or myeloid Ffar2 gene deletion inhibited lung carcinogenesis and syngeneic tumor growth, reducing MDSCs and increasing CD8+ T-cell infiltration [2]. In addition, NaB-mediated ferroptosis promotion was related to FFAR2-mTORC1 axis, and NaB treatment's effect on tumor growth was mTOR-dependent [3]. Mice lacking ffar2 showed reduced SCFA-triggered GLP-1 secretion and impaired glucose tolerance [4]. Targeted activation of FFAR2 decreased susceptibility to various infections [5]. Ffar2-deficient mice had microglia defects similar to germ-free conditions [7]. Decreasing Ffar2 expression in leukaemic cells promoted their growth in vivo [8].

In conclusion, Ffar2 is essential for maintaining gut homeostasis, regulating immune responses, and influencing metabolic processes. KO/CKO mouse models have revealed its role in diseases such as colonic injury, cancer, diabetes, infections, CNS-related microglia disorders, and leukaemia. Understanding Ffar2 functions through these models provides potential therapeutic targets for these diseases.