S100A8 and S100A9 belong to a family of 25 homologous low-molecular-weight intracellular calcium-binding proteins that exhibit tissue and cell-specific expression. They are characterized by two distinct EF-hand (helix-loop-helix) calcium-binding domains connected by a hinge region. The N-terminal Ca2+ binding domain has lower affinity than the canonical C-terminal domain that allows for functionally important second messenger roles dependent on intracellular Ca2+ levels. Human S100A8 (also known as MRP8, calgranulin A, L1 light chain, cystic fibrosis antigen) is the most closely related member of the human (h) S100 family to mS100A8, although the level of homology is low (69% at the DNA level; 58% at the amino acid level). Human S100A8 is a calcium-binding protein member of the S100 protein family, is highly expressed in the cytosol of neutrophils and monocytes, and is frequently found at high levels in the extracellular milieu during inflammatory conditions. S100A8 is almost exclusively expressed by cells of myeloid lineage and is constitutively expressed in the cytosol of neutrophils. Monocytes and differentiated macrophages from inflamed tissues also express S100A8. Increased serum levels of the S100A8 (MRP-8) protein have been reported in inflammatory conditions including bacterial infection, arthritis, and cystic fibrosis (CF). Preferentially exists as a heterodimer or heterotetramer with S100A9 known as calprotectin (S100A8/A9). Calprotectin (S100A8/9) is predominantly expressed in myeloid cells. Except for inflammatory conditions, the expression is restricted to a specific stage of myeloid differentiation since both proteins are expressed in circulating neutrophils and monocytes but are absent in normal tissue macrophages and lymphocytes. Under chronic inflammatory conditions, such as psoriasis and malignant disorders, also expressed in the epidermis. Found in high concentrations at local sites of inflammation or in the serum of patients with inflammatory diseases such as rheumatoid, cystic fibrosis, inflammatory bowel disease, Crohn's disease, giant cell arteritis, cystic fibrosis, Sjogren's syndrome, systemic lupus erythematosus, and progressive systemic sclerosis. Involved in the formation and deposition of amyloids in the aging prostate known as corpora amylacea inclusions. Strongly up-regulated in many tumors, including gastric, esophageal, colon, pancreatic, bladder, ovarian, thyroid, breast and skin cancers.