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The ion channel TRPV6 is likely to function as an epithelial calcium channel in organs with high calcium transport requirements such as the intestine, kidney, and placenta. Transcriptional regulation of TRPV6 messenger RNA (mRNA) is controlled by 1,25-dihydroxyvitamin D, which is the active hormonal form of vitamin D3, and by additional calcium-dependent and vitamin D3-independent mechanisms. Under physiological conditions, the conductance of the channel itself is highly calcium-selective and underlies complex inactivation mechanisms triggered by intracellular calcium and magnesium ions. There is growing evidence that transcriptional regulation of TRPV6 in certain tissues undergoing malignant transformation, such as prostate cancer, is linked to cancer progression.