Mincle, the macrophage-inducible C-type lectin also known as CLEC-4E, binds to the mycobacterial glycolipid trehalose dimycolate and initiates a signaling cascade by serving as a receptor for Mycobacterium tuberculosis and other pathogenic mycobacterial species. Studies of the biological functions of human mincle often rely on mouse models, based on the assumption that the biological properties of the mouse receptor mimic those of the human protein. Experimental support for this assumption has been obtained by expression of the carbohydrate-recognition domain of mouse mincle and characterization of its interaction with small molecule analogs of trehalose dimycolate. The results confirm that the ligand-binding properties of mouse mincle closely parallel those of the human receptor. These findings are consistent with the conservation of key amino acid residues that have been shown to form the ligand-binding site in human and cow mincle. Sequence alignment reveals that these residues are conserved in a wide range of mammalian species, suggesting that mincle has a conserved function in binding ligands that may include endogenous mammalian glycans or pathogen glycans in addition to trehalose dimycolate.