calbindinD9k

Calbindin-D9k, also known as calbindin 9-kDa and encoded by the S100G gene, is a small cytosolic calcium-binding protein of the EF-hand family. It is approximately 9 kDa in mass and contains two EF-hand motifs that coordinate calcium ions. The protein functions mainly as an intracellular calcium buffer and shuttle, aiding the rapid and safe movement of Ca2+ within cells.

Expression of calbindin-D9k is highest in the mucosa of the small intestine, particularly in duodenal and jejunal enterocytes, and is present to a lesser extent in the kidney. Its intestinal expression is strongly stimulated by 1,25-dihydroxyvitamin D3 (calcitriol) through the vitamin D receptor, placing calbindin-D9k within the vitamin D–dependent pathway of transcellular calcium absorption.

In the intestinal epithelium, calcium enters cells via apical channels such as TRPV6, binds to calbindin-D9k in the cytosol, and is delivered to the basolateral membrane where extrusion occurs through Ca2+-ATPases (e.g., PMCA1b) and exchangers (NCX1). By buffering and guiding Ca2+, calbindin-D9k enhances transcellular transport and protects cells from calcium toxicity. In the kidney, the protein participates in intracellular calcium handling in segments involved in reabsorption.

Clinical and research notes indicate that loss or reduced expression of S100G/calbindin-D9k in animal models impairs intestinal calcium absorption and can affect bone mineralization, especially under low dietary calcium. In humans, variation in expression typically influences calcium homeostasis in the context of vitamin D status rather than causing a primary disease. Calbindin-D9k is frequently used as a molecular marker of vitamin D action in intestinal studies.