Calcium ions (Ca2+) play a pivotal role in the physiology and biochemistry of organisms and the cell. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction of all muscle cell types, and in fertilization. Many enzymes require calcium ions as a cofactor, those of the blood-clotting cascade being notable examples. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation.

Calcium-binding proteins are proteins that participate in calcium cell signalling pathways by binding to Ca2+. Many different calcium-binding proteins exist, with different cellular and tissue distribution and involvement in specific functions. The most ubiquitous Ca2+-sensing protein, found in all eukaryotic organisms including yeasts, is calmodulin.

Compartmentalization of calcium binding proteins has been noted within cells, suggesting that these proteins perform distinct functions in localized calcium signaling. It also indicates that in addition to freely diffusing through the cytoplasm to attain a homogeneous distribution, calcium binding proteins can bind to cellular structures through interactions that are likely important for their functions.