{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T21:23:07Z","timestamp":1787606587802,"version":"build-2736575974"},"reference-count":112,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The vitamin D receptor (VDR) is a ligand-activated nuclear receptor that mediates the biological actions of vitamin D and is a critical regulator of mineral homeostasis, cellular differentiation, immune function, and metabolism. VDR is a high-affinity intracellular binding protein for the most active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25D). Early biochemical and molecular studies established VDR as a member of the nuclear receptor superfamily, functioning as a transcription factor that heterodimerizes with the retinoid X receptor and binds vitamin D response elements to regulate gene expression. Since the cloning of the VDR gene in the 1980s, characterization of its structural domains and identification of coregulators significantly advanced understanding of its genomic mechanisms of action. Over the past several decades, research has expanded the scope of VDR biology beyond classical calcium and phosphate metabolism. Genome-wide binding analyses and transcriptomic studies have revealed extensive VDR cistromes and context-dependent gene networks across diverse tissues. These advances have positioned VDR as a key factor linking vitamin D availability to tissue-specific outcomes. Despite substantial progress, fundamental questions remain, including mechanisms governing tissue-specific VDR actions, integration of genomic signaling pathways, and the role of VDR in complex diseases, such as cancer, autoimmune disorders, and aging. In addition, how VDR function is modulated by chromatin context, metabolic state, and the microbiome remains incompletely understood. Here, we summarize what is known about these actions of VDR and its history of discovery. Addressing these questions will be essential for translating mechanistic insights into improved therapeutic strategies targeting the vitamin D axis.<\/jats:p>","DOI":"10.1530\/joe-26-0204","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T15:49:58Z","timestamp":1786031398000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":0,"title":["The vitamin D receptor story: discovery, control, and genomic reach"],"prefix":"10.1530","volume":"270","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6612-7491","authenticated-orcid":true,"given":"Mark B","family":"Meyer","sequence":"first","affiliation":[{"name":"Department of Food and Nutritional Sciences, University of Wisconsin-Madison 1 , , ,","place":["Madison, Wisconsin, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Wesley","family":"Pike","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin-Madison 2 , , ,","place":["Madison, Wisconsin, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"2026082416565787800_bib1","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1172\/JCI88887","article-title":"The vitamin D receptor: contemporary genomic approaches reveal new basic and translational insights","volume":"127","author":"Pike","year":"2017","journal-title":"J Clin Investig"},{"key":"2026082416565787800_bib2","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1126\/science.3029866","article-title":"Molecular cloning of complementary DNA encoding the avian receptor for vitamin D","volume":"235","author":"McDonnell","year":"1987","journal-title":"Science"},{"key":"2026082416565787800_bib3","doi-asserted-by":"crossref","first-page":"3294","DOI":"10.1073\/pnas.85.10.3294","article-title":"Cloning and expression of full-length cDNA encoding human vitamin D receptor","volume":"85","author":"Baker","year":"1988","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026082416565787800_bib4","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1359\/jbmr.1998.13.3.325","article-title":"The nuclear vitamin D receptor: biological and molecular regulatory properties revealed","volume":"13","author":"Haussler","year":"1998","journal-title":"J Bone Miner Res"},{"key":"2026082416565787800_bib5","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/bs.vh.2015.10.011","article-title":"Genomic determinants of vitamin D-regulated gene expression","volume":"100","author":"Pike","year":"2016","journal-title":"Vitam Horm"},{"key":"2026082416565787800_bib6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.jsbmb.2013.11.004","article-title":"Fundamentals of vitamin D hormone-regulated gene expression","volume":"144","author":"Pike","year":"2014","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2026082416565787800_bib7","doi-asserted-by":"crossref","first-page":"4055","DOI":"10.1016\/S0021-9258(18)93278-3","article-title":"The association of a metabolite of vitamin D3 with intestinal mucosa chromatin in vivo","volume":"243","author":"Haussler","year":"1968","journal-title":"J Biol Chem"},{"key":"2026082416565787800_bib8","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1073\/pnas.62.1.155","article-title":"Chromosomal receptor for a vitamin D metabolite","volume":"62","author":"Haussler","year":"1969","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026082416565787800_bib9","doi-asserted-by":"crossref","first-page":"4871","DOI":"10.1073\/pnas.72.12.4871","article-title":"Cytoplasmic and nuclear binding components for 1a25-dihydroxyvitamin D3 in chick parathyroid glands","volume":"72","author":"Brumbaugh","year":"1975","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026082416565787800_bib10","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0024-3205(75)90256-8","article-title":"Nuclear and cytoplasmic binding components for vitamin D metabolites","volume":"16","author":"Brumbaugh","year":"1975","journal-title":"Life Sci"},{"key":"2026082416565787800_bib11","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1126\/science.183.4129.1089","article-title":"Radioreceptor assay for 1 alpha,25-dihydroxyvitamin D3","volume":"183","author":"Brumbaugh","year":"1974","journal-title":"Science"},{"key":"2026082416565787800_bib12","doi-asserted-by":"crossref","first-page":"5485","DOI":"10.1073\/pnas.76.11.5485","article-title":"Purification of chicken intestinal receptor for 1,25-dihydroxyvitamin D","volume":"76","author":"Pike","year":"1979","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026082416565787800_bib13","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1016\/S0021-9258(18)33191-0","article-title":"Serum and monoclonal antibodies against the chick intestinal receptor for 1,25-dihydroxyvitamin D3. 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