Publisher Summary This chapter discusses the tissue distribution, structure, and functions of macrophage lectin. This has not been established by immunohistological techniques; however RNA analysis suggests that in the mouse, the molecule is expressed at low levels by resident peritoneal macrophages and is upregulated on thioglycollate-elicited peritoneal macrophages. Similarly, in the rat, the antigen appears to be restricted to macrophages. Human macrophage lectin (HML) is a type II transmembrane molecule containing a single extracellular C-type lectin domain. It is the homolog of the rat macrophage asialoglycoprotein receptor (M-ASGP-BP), the mouse macrophage galactose/N-acetylgalactosamine-specific lectin (MMGL) and is closely related to other human C-type lectins. The C-type lectin domains have the greatest similarity: 69% between HML and HHL-1, and 63% between HML and HHL-2. The cytoplasmic domains of the lectins are more poorly conserved. The presence of a YENF internalization motif in the cytoplasmic domain suggests that the lectin is likely to be involved in receptor-mediated endocytosis. Recombinant HML expressed in E. coli has been shown to strongly bind glycopeptides carrying three consecutive N-acetylgalactosamine-Ser/Thr residues known as Tn antigen, which is a human carcinoma-associated epitope, implicating a role in recognition by tumoricidal macrophages.