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Structurally, Piezo1 features a distinctive trimeric propeller structure that undergoes conformational changes in response to membrane tension, enabling mechanogating. Accordingly, Piezo1 is involved in a broad spectrum of physiological processes, including vascular development and homeostasis, bone and cartilage formation, skeletal muscle growth, neural development, sensory perception, immune regulation, and cellular volume regulation. Accumulating evidence indicates that mutations or dysregulation of Piezo1 are closely associated with a variety of human diseases, including genetic diseases, cardiovascular diseases, infectious diseases, autoimmune diseases, and cancer. Therefore, Piezo1 has emerged as a potential therapeutic target. Currently, the exploration of pharmacological modulators targeting Piezo1, as well as emerging approaches such as gene therapy, artificial intelligence (AI)-driven drug discovery, and advanced drug delivery systems, offer potential avenues for the development of Piezo1-targeted therapeutic strategies. However, these approaches still face significant challenges regarding specificity, in vivo targeting, and context-dependent effects. This review systematically summarizes the structure, mechanogating mechanisms, physiological and cellular functions of Piezo1, as well as its associations with human diseases. Based on this, the limitations of current Piezo1-targeted therapeutic strategies and their future developmental directions are highlighted, while the therapeutic potential of targeting Piezo1 is emphasized.<\/jats:p>","DOI":"10.1186\/s43556-026-00549-7","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T09:42:46Z","timestamp":1787132566000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Piezo1 channel: structure, mechanogating mechanism, functions, diseases and therapeutic strategy"],"prefix":"10.1186","volume":"7","author":[{"given":"Qixiang","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuqiang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiongyu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinguo","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7395-0451","authenticated-orcid":false,"given":"Tao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"issue":"11","key":"549_CR1","doi-asserted-by":"publisher","first-page":"1758","DOI":"10.1016\/j.neuron.2025.04.015","volume":"113","author":"C Santiago","year":"2025","unstructured":"Santiago C, Siegrist J, Africawala N, Handler A, Tasnim A, Anjum R, et al. 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