S100A6 (calcyclin) is a 10.5 kDa Ca2+-binding protein that belongs to the S100 protein family. S100A6 contains two EF-hand motifs responsible for binding of Ca2+. It also binds Zn2+ through not yet identified structures. Binding of Ca2+ induces a conformational change in the S100A6 molecule which in consequence increases its overall hydrophobicity and allows for interaction with target proteins. S100A6 was found in different mammalian and avian (chicken) tissues. A high level of S100A6 is observed in epithelial cells, fibroblasts and in different kinds of cancer cells. The function of S100A6 is not clear at present, but it has been suggested that it may be involved in cell proliferation, cytoskeletal dynamics and tumorigenesis. Additionally, S100A6 might have some extracellular activities. This review presents new facts and features concerning the S100A6 protein. (C) 2009 Elsevier Inc. All rights reserved.