Calbindin-$D_{9k}$ (CaBP-9k), a cytosolic calcium-binding protein, is expressed in a variety of tissues, i.e., the duodenum, uterus, placenta, kidney and pituitary gland. Duodenal CaBP-9k is involved in intestinal calcium absorption, and is regulated at transcriptional and post-transcriptional levels by 1,25-dihydroxyvitamin D3, the hormonal form of vitamin D, and glucocorticoids (GCs). Uterine CaBP-9k has been implicated in the regulation of myometrial action(s) through modulation of intracellular calcium, and steroid hormones appear to be the main regulators in its uterine and placental regulation. Because phenotypes of CaBP-9k-null mice appear to be normal, other calcium-transporter genes may compensate for its gene deletion and physiological function in knockout mice. Previous studies indicate that CaBP-9k may be controlled in a tissue-specific fashion. In this review, we summarize the current information on calcium homeostasis related to CaBP-9k gene regulation by GCs, vitamin D and its receptors, and its molecular regulatory mechanism. In addition, we present related data from our current research.