Calnuc is a recently discovered multidomain protein with EF-hand calcium binding sites. Several studies have reported various interacting partners for calnuc and, therefore, also different sites of localization in the cell. It interacts with important molecules such as DNA, G protein, COX, and amyloid precursor protein among others in addition to being involved in stress response and trafficking. The immense possibilities (of various functions this protein might be involved in) implicate great future in medicine and physiology. Preliminary studies also implicate the possibility of calnuc being involved in some of the human diseases. These initial observations imply the functions that this protein might be involved in. This review emphasizes the importance of further research on this protein. © 2010 IUBMB.