The canonical molecular pathway of vitamin D is mediated by an active vitamin D metabolite, 1,25-dihydroxyvitamin D
3 (1,25D
3), which is bound to vitamin D receptor (VDR). Recently, novel molecular mechanisms underlying the actions of vitamin D, including the VDR-independent action of 1,25D
3 and the direct action of 25-hydroxyvitamin D
3 (25D
3, a precursor of 1,25D
3), which interacts with and without VDR, have been reported. Further elucidation of these novel mechanisms may bring a paradigm shift in vitamin D-related research. This review aims to provide recent evidence concerning the novel molecular mechanisms of action of 25D
3 which have been elucidated by several research groups including our group.
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