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However, because both deficiency and excess can cause severe pathology, precise regulation is critical. The liver plays a central role in systemic iron metabolism, and growing evidence identifies hepatic iron dyshomeostasis as a key catalyst in diverse liver disorders, including metabolic dysfunction\u2010associated steatotic liver disease (MASLD\/MASH), alcoholic liver disease, liver fibrosis, and hepatocellular carcinoma (HCC). Hepatic iron accumulation promotes liver injury primarily through oxidative stress, mitochondrial dysfunction, and ferroptosis. In this review, we synthesize the multi\u2010layered regulatory landscape of hepatic iron homeostasis, encompassing systemic coordination, cellular fine\u2010tuning, and epigenetic modifications. We thoroughly dissect the pathogenic impact of iron overload and critically evaluate emerging therapeutic strategies aimed at restoring iron balance, such as hepcidin mimetics and ferroptosis modulators. Finally, we discuss current literature gaps\u2014including preclinical model limitations, the lack of standardized non\u2010invasive biomarkers, and drug delivery bottlenecks\u2014providing a clear roadmap for future translational research in iron\u2010related liver pathologies.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.71412","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:34:49Z","timestamp":1792643689000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Iron Homeostasis and Liver Diseases"],"prefix":"10.1111","volume":"30","author":[{"given":"Peng","family":"Yang","sequence":"first","affiliation":[{"name":"School of Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases Yunnan University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4393-886X","authenticated-orcid":false,"given":"Zhitian","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Hepatopancreatobiliary Surgery The Second Affiliated Hospital of Kunming Medical University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases Yunnan University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0346-0263","authenticated-orcid":false,"given":"Zhihong","family":"Tu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases Yunnan University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases Yunnan University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatopancreatobiliary Surgery The Second Affiliated Hospital of Kunming Medical University  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6152-7963","authenticated-orcid":false,"given":"Yonglong","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Yunnan Key Laboratory of Cell Metabolism and Diseases Yunnan University  Kunming Yunnan China"},{"name":"Southwest United Graduate School  Kunming Yunnan China"},{"name":"Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province  Kunming Yunnan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","DOI":"10.3390\/min16010047","article-title":"A Novel Biomass\u2010Derived Reductant for Nitric Acid Dissolution of Manganiferous Iron Ore: Comparative Assessment of Organic Reductants","volume":"16","author":"Top S.","year":"2026","journal-title":"Minerals"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","DOI":"10.3390\/nu15112441","article-title":"Nutritional Aspects of Iron in Health and Disease","volume":"15","author":"Charlebois E.","year":"2023","journal-title":"Nutrients"},{"key":"e_1_2_12_4_1","doi-asserted-by":"crossref","first-page":"20441","DOI":"10.1021\/acsomega.2c01833","article-title":"Iron Absorption: Factors, Limitations, and Improvement Methods","volume":"7","author":"Piskin E.","year":"2022","journal-title":"ACS Omega"},{"key":"e_1_2_12_5_1","doi-asserted-by":"crossref","first-page":"3641","DOI":"10.1002\/j.2040-4603.2022.tb00226.x","article-title":"Paying the Iron Price: Liver Iron Homeostasis and Metabolic Disease","volume":"12","author":"Ameka M.","year":"2022","journal-title":"Comprehensive Physiology"},{"key":"e_1_2_12_6_1","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2024.1494527","article-title":"A Decade of Iron Overload Disorders and Hemochromatosis: Clinical and Genetic Findings From a Specialized Center in Colombia","volume":"11","author":"Cristancho L. 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