Calcium ions regulate many processes in the central nervous system via interaction with intracellular calcium-binding proteins. One class of these proteins shares a common structural motif, the EF-hand. A consensus amino acid sequence for this motif has aided the identification of many new members of this family. Some of these proteins, like parvalbumin, calbindin, and calretinin, proved to be useful neuronal markers for a variety of functional brain systems and their circuitries. Their major role is assumed to be buffering, transport of Ca2+, and regulation of various enzyme systems. Cellular degeneration is often accompanied by Ca2+ overload. It has been assumed that neurons containing certain intracellular Ca(2+)-binding proteins may have a greater capacity to buffer Ca2+ and therefore would be more resistant to degeneration.