MD2 together with Toll-like receptor 4 (TLR4) is one of the key pattern recognition receptors for a pathogen-associated molecular pattern and activates innate immunity by recognizing lipopolysaccharide (LPS) of Gram-negative bacteria. MD-2 enabled TLR4 to respond to a wide variety of LPS partial structures, Gram-negative bacteria, and Gram-positive lipoteichoic acid, but not to Gram-positive bacteria, peptidoglycan, and lipopeptide.