CD24 is a highly glycosylated protein expressed as glycosyl-phosphatidyl-inositol (GPI) anchored molecule. Widely expressed, mainly on T cells, B cells and is upregulated in numerous types of cancers. It has costimulatory activity for antigen specific T cell responses. Polymorphisms of human CD24 are associated with several autoimmune diseases. Recently a new role as negative regulator of the immune response has been reported. CD24-deficient mice are more sensitive to inflammatory responses. CD24 together with the membrane protein SIGLEC interacts with danger-associated molecular patterns (DAMPs), such as HMGB1, HSP90 or HSP70. CD24/SIGLEC complex may differentially regulate the host response to DAMPs and PAMPs (pathogen-associated molecular patterns).