{
  "abstract": "Adenosine 5’-monophosphate−activated protein kinase (AMPK), a highly conserved energy-sensing kinase, plays a central role in maintaining cellular metabolic homeostasis, such as glucose/lipid metabolism, mitochondrial biogenesis, and autophagy, to counteract energetic stress. Beyond the canonical adenylate-dependent activation of AMPK by sensing the ATP:AMP/ADP ratio, emerging evidence reveals noncanonical activation mechanisms. Proper AMPK signaling is essential for physiological functions, whereas its dysregulation underlies various pathologies, including metabolic diseases, immune disorders, and cancer. This review systematically recapitulates the historical background and landmark discoveries of the AMPK field, including the discovery of AMPK, the structure of AMPK complex, upstream regulators and downstream substrates, and the transcriptional/posttranscriptional and posttranslational regulatory mechanisms. Furthermore, we delineate its roles in maintaining metabolic equilibrium, mitochondrial integrity, and immune competence across organ systems and highlight how dysregulated AMPK activity contributes to pathological diseases, encompassing alterations in its expression levels, intrinsic kinase activity, subcellular localization or upstream regulatory signaling cascades. Specifically, we focus on knock-in or knockout mouse models utilized to study AMPK-associated human diseases and the translational potential of AMPK-targeting agonists or antagonists across diverse pathological conditions. A deep understanding of the multidimensional regulatory network of AMPK and mechanistic insights with therapeutic innovations that we provide with this review will help address the challenges of complex metabolic diseases.",
  "abstract_shown": true,
  "affiliations": [
    "The First Affiliated Hospital of Soochow University, the Institutes of Biology and Medical Sciences, Suzhou Medical College, Soochow University, Suzhou, China",
    "Biomedical Basic Research Center of Jiangsu, Soochow University, Suzhou, China",
    "Department of Gynecological Oncology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, China",
    "Department of Rheumatology and Immunology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China",
    "Life Sciences Institute and State Key Laboratory of Transvascular Implantation Devices of the Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China",
    "The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China",
    "Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu, China",
    "Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhengkui Zhang"
    },
    {
      "affs": [
        2
      ],
      "name": "Yuanzhuo Gu"
    },
    {
      "affs": [
        0
      ],
      "name": "HongChao He"
    },
    {
      "affs": [
        0
      ],
      "name": "Shilei Qiao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yifan Shao"
    },
    {
      "affs": [
        3
      ],
      "name": "Xianming Long"
    },
    {
      "affs": [
        4
      ],
      "name": "Jun Huang",
      "orcid": "0000-0002-7837-653X"
    },
    {
      "affs": [
        4,
        5,
        6
      ],
      "name": "Long Zhang",
      "orcid": "0000-0001-8139-0474"
    },
    {
      "affs": [
        0,
        1,
        2,
        7
      ],
      "name": "Fangfang Zhou",
      "orcid": "0000-0003-1870-7584"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5rva5p6hwj0ar.bib",
  "cited_by": 0,
  "doi": "10.1038/s41392-026-02790-6",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710858/",
  "id": "5rva5p6hwj0ar",
  "issns": [
    "2095-9907",
    "2059-3635"
  ],
  "landing_url": "https://doi.org/10.1038/s41392-026-02790-6",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review Article"
    ],
    [
      "openalex",
      "1312|Metabolism, Diabetes, and Cancer"
    ]
  ],
  "openalex": "W7223698193",
  "pdf_url": null,
  "pmcid": "PMC13710858",
  "pmid": "42934234",
  "published": "2026-10-27",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/5rva5p6hwj0ar.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:44Z",
      "native_id": "PMC13710858",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41392-026-02790-6"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Metabolism, Diabetes, and Cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "The AMPK signaling pathway in cell metabolism and human diseases",
  "title_text": "The AMPK signaling pathway in cell metabolism and human diseases",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:44Z",
  "url": "https://research.draconitic.com/paper/5rva5p6hwj0ar",
  "venue": "Signal Transduction and Targeted Therapy",
  "versions": []
}