Regucalcin is a Ca2+ binding protein that is encoded by a highly conserved gene in vertebrate species. Regucalcin is greatly expressed in liver and kidney cortex, and the expression is mediated through a Ca2+ signaling mechanism with AP1 and NFI-A1 as transcriptional factors. It plays a multifunctional role as a regulatory protein in intracellular signaling processes in the cytoplasm and nucleus of cells including the maintenance of intracellular Ca2+ homeostasis, the regulation of various Ca2+ dependent protein kinases and tyrosine kinases, protein phosphatases, nitric oxide (NO) synthase, and the suppression of nuclear DNA and RNA syntheses. Regucalcin has suppressive effects on cell proliferation, cell death and apoptosis, and is suggested to play a physiologic role in the maintenance of cellular homeostasis.