Clec4f, encoding a C-type lectin receptor, is specifically expressed by Kupffer cells in mice. It recognizes desialylated glycans and is involved in multiple biological functions. CLEC4F has diverse binding specificities to sugars like galactose, N-acetylgalactosamine, and is involved in processes such as pathogen recognition and antigen presentation [1,2,3].

In the study of desialylated platelet destruction, Clec4f-/-mouse models revealed that CLEC4F on Kupffer cells is crucial for mediating the destruction of desialylated platelets in the liver in vivo [1]. In visceral leishmaniasis, early-stage granulomas predominantly consisted of CLEC4F + KCs, and late-stage granulomas led to KCs downregulating CLEC4F, showing its association with granuloma maturation and hepatic immunity [4]. Also, in cystic echinococcosis, the uptake of parasite-derived mucins by Kupffer cells is largely dependent on Clec4F [5].

In conclusion, Clec4f is essential for Kupffer-cell-specific functions such as platelet destruction, antigen presentation, and the handling of parasite-derived materials. Gene-knockout mouse models have been instrumental in revealing its role in diseases like thrombocytopenia during sepsis, visceral leishmaniasis, and cystic echinococcosis, providing insights into disease mechanisms and potential therapeutic targets.