S100 calcium-binding protein G (S100G) (S100G)

S100 calcium-binding protein G, commonly known as Calbindin-D9k, is a low-molecular-weight protein belonging to the S100 family of EF-hand calcium-binding proteins (UniProt). It is primarily recognized for its role in the small intestine, where it facilitates the transcellular transport of calcium and acts as a cytosolic buffer to maintain low levels of free calcium, thereby preventing cellular toxicity (PubMed, PMC). Its expression is highly regulated by vitamin D (calcitriol) in the intestine and by sex steroids like estrogen in the uterus and pituitary gland (PMC). Beyond its classical role in mineral homeostasis, Calbindin-D9k has emerged as a significant factor in neuroprotection; studies in knockout models show that its absence leads to increased accumulation of amyloid-beta and alpha-synuclein, as well as endoplasmic reticulum stress-induced apoptosis, linking it to the pathogenesis of Alzheimer's and Parkinson's diseases (PubMed). Additionally, it serves as a sensitive biomarker for detecting the activity of estrogenic endocrine disruptors (PubMed). Therapeutic strategies involving this target focus on restoring calcium homeostasis or mitigating ER stress, often using agents like tauroursodeoxycholic acid in experimental models (PMC).

Other names

Calbindin-D9kCalbindin-3CholecalcinVitamin D-dependent calcium-binding protein, intestinalCABP9K9 kDa CaBP

Transcriptional induction via vitamin D receptor (VDR) or estrogen receptor (ER) signaling; modulation of intracellular calcium buffering and transcellular transport.