Calbindin contains 4 active calcium-binding domains, and 2 modified domains that have lost their calcium-binding capacity. Calbindin acts as a calcium buffer and calcium sensor and can hold four Ca2+ in the EF-hands of loops EF1, EF3, EF4 and EF5. Calbindin is a vitamin D–responsive gene in many tissues, in particular the chick intestine, where it has a clear function in mediating calcium absorption. In the brain, its synthesis is independent of vitamin-D. Although it was originally proposed that the major role of calbindin is to facilitate the vitamin D dependent movement of calcium through the cytosolic compartment of the intestinal or renal cell, it was found that calbindin also has a major role in different cell types in protecting against apoptotic cell death.