Host defense by lectins is a universal immune system from prokaryotes to mammals. During evolution, vertebrates have acquired lectin receptors that are expressed as transmembrane proteins and initiate immune responses by recognizing ligands [1]. Macrophage-inducible C-type lectin (Mincle, gene name CLEC4E) is one such lectin receptor and an immune activation receptor expressed in monocytes and macrophages. Mincle recognizes exogenous glycolipids derived from pathogens such as Mycobacterium tuberculosis and triggers immune responses (Fig. 74.1a). Also, Mincle recognizes endogenous ligands derived from damaged self, making it an important protein involved in genetic diseases and chronic inflammation.