{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T18:07:20Z","timestamp":1792606040461,"version":"4.5.0"},"reference-count":131,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T00:00:00Z","timestamp":1761264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>CYP24A1, a mitochondrial cytochrome P450 enzyme, plays a critical role in the catabolism of active vitamin D metabolites and is a key regulator of local vitamin D signaling in the small intestine. While traditionally studied in the context of renal physiology, increasing evidence highlights its distinct regulatory mechanisms and functional significance within the intestinal epithelium. This review explores the molecular architecture, tissue-specific expression patterns, and multifactorial regulation of CYP24A1 in enterocytes, encompassing nuclear receptor signaling, epigenetic and post-transcriptional control, and environmental influences such as inflammation, diet, and the gut microbiota. We discuss how intestinal CYP24A1 modulates the expression of vitamin D target genes involved in transcellular calcium absorption and epithelial barrier function, and how its dysregulation contributes to gastrointestinal disorders including inflammatory bowel diseases, celiac disease, microbiota dysbiosis, and colorectal cancer. In addition, we examine preclinical and translational evidence supporting CYP24A1 as a potential therapeutic target. Emerging strategies such as selective enzyme inhibitors, microbiota modulation, RNA-based technologies, and personalized supplementation approaches are considered in the context of restoring local vitamin D bioactivity and mineral homeostasis. Together, this review underscores the clinical importance of intestinal CYP24A1 and highlights novel opportunities for targeted interventions in vitamin D-responsive gastrointestinal pathologies.<\/jats:p>","DOI":"10.3390\/nu17213348","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T07:31:58Z","timestamp":1761550318000},"page":"3348","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["CYP24A1 in Small Intestinal Vitamin D Metabolism and Clinical Implications"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5848-8788","authenticated-orcid":false,"given":"Agnieszka","family":"Nowacka","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Nicolaus Copernicus University in Toru\u0144, Collegium Medicum in Bydgoszcz, ul. Curie Sk\u0142odowskiej 9, 85-094 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"\u015aniegocki","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Nicolaus Copernicus University in Toru\u0144, Collegium Medicum in Bydgoszcz, ul. Curie Sk\u0142odowskiej 9, 85-094 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7517-2075","authenticated-orcid":false,"given":"Dominika","family":"Bo\u017ci\u0142ow","sequence":"additional","affiliation":[{"name":"Anaesthesiology and Intensive Care Clinical Ward, The 10th Military Research Hospital and Polyclinic, ul. Powsta\u0144c\u00f3w Warszawy 5, 85-681 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1822-3133","authenticated-orcid":false,"given":"Ewa A.","family":"Zi\u00f3\u0142kowska","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, Washington University in St. Louis, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Carlberg, C., Raczyk, M., and Zawrotna, N. (2023). Vitamin D: A master example of nutrigenomics. Redox Biol., 62.","DOI":"10.1016\/j.redox.2023.102695"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Saponaro, F., Saba, A., and Zucchi, R. (2020). An Update on Vitamin D Metabolism. Int. J. Mol. 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