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Transporters play a critical role in mediating the uptake of metal ions, including Cd. However, a substantial number of Cd transporters in rice remain uncharacterized. In this study, we identify OsMDR4, a member of the multidrug resistance protein family, as a mediator of Cd uptake in rice. Heterologous overexpression of OsMDR4 in yeast increased both Cd sensitivity and intracellular Cd accumulation. Consistent with this, the Cd concentrations in both roots and shoots of the mdr4 mutants were significantly lower than those in wild type. Kinetic analysis further revealed that the maximum Cd uptake rate in mdr4 mutants was markedly reduced compared with wild type. Expression analysis showed that OsMDR4 is primarily expressed in the epidermis and root hairs of rice seedlings and in floral organs during the flowering stage. Notably, OsMDR4 expression in seedling roots was upregulated in response to Cd exposure. Subcellular localization analysis revealed that OsMDR4\u2013EGFP was predominantly localized to the plasma membrane in a heterologous Arabidopsis protoplast system. In summary, we have identified and characterized OsMDR4 as a previously uncharacterized protein that contributes to cadmium accumulation in rice.<\/jats:p>","DOI":"10.3390\/plants15152378","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T10:24:07Z","timestamp":1785752647000},"page":"2378","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Multidrug Resistance Protein OsMDR4 Is Involved in Cadmium Absorption in Rice (Oryza sativa L.)"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7402-0359","authenticated-orcid":false,"given":"Zijing","family":"Xie","sequence":"first","affiliation":[{"name":"Hunan Provincial Key Laboratory of the Traditional Chinese Medicine Agricultural Biogenomics, Changsha Medical University, Changsha 410219, China"},{"name":"Hunan Province Key Laboratory of Crop Sterile Germplasm Resource Innovation and Application, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Hao","sequence":"additional","affiliation":[{"name":"Hunan Province Key Laboratory of Crop Sterile Germplasm Resource Innovation and Application, College of Life Sciences, Hunan Normal University, Changsha 410081, China"},{"name":"College of Life and Environmental Science, Hunan University of Arts and Science, Changde 415000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Hunan Province Key Laboratory of Crop Sterile Germplasm Resource Innovation and Application, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Lei","sequence":"additional","affiliation":[{"name":"Hunan Province Key Laboratory of Crop Sterile Germplasm Resource Innovation and Application, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinzhou","family":"Jin","sequence":"additional","affiliation":[{"name":"Hunan Province Key Laboratory of Crop Sterile Germplasm Resource Innovation and Application, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Wu","sequence":"additional","affiliation":[{"name":"Hunan Province Key Laboratory of Crop Sterile Germplasm Resource Innovation and Application, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Hu","sequence":"additional","affiliation":[{"name":"Hunan Province Key Laboratory of Crop Sterile Germplasm Resource Innovation and Application, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianfu","family":"Tian","sequence":"additional","affiliation":[{"name":"Hunan Province Key Laboratory of Crop Sterile Germplasm Resource Innovation and Application, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongping","family":"Li","sequence":"additional","affiliation":[{"name":"Hunan Province Key Laboratory of Crop Sterile Germplasm Resource Innovation and Application, College of Life Sciences, Hunan Normal University, Changsha 410081, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1016\/j.biochi.2006.10.001","article-title":"Cadmium: Cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review)","volume":"88","author":"Bertin","year":"2006","journal-title":"Biochimie"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S1470-2045(06)70545-9","article-title":"Environmental exposure to cadmium and risk of cancer: A prospective population-based study","volume":"7","author":"Nawrot","year":"2006","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1111\/j.1744-7909.2008.00737.x","article-title":"How Plants Cope with Cadmium: Staking All on Metabolism and Gene Expression","volume":"50","author":"DalCorso","year":"2008","journal-title":"J. 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