{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:51:38Z","timestamp":1790351498788,"version":"4.1.0"},"reference-count":140,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82570896"],"award-info":[{"award-number":["82570896"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470796"],"award-info":[{"award-number":["82470796"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Nephrolithiasis is a prevalent urological disorder worldwide, whose pathogenesis involves a complex network of crystal formation, cellular injury, and microenvironmental dysregulation. As a critical mechanism for regulating cellular functions, protein post-translational modifications (PTMs) have been increasingly implicated in multiple facets of kidney stone formation, including crystal\u2013cell interactions, oxidative stress responses, and inflammatory signaling pathways. This review systematically synthesizes the biochemical foundations of PTMs, the molecular microenvironment of nephrolithiasis, and the roles of key modifications such as phosphorylation and acetylation in the pathogenesis of calculi. It further explores the translational potential of PTM detection technologies in clinical practice. Current evidence indicates that PTMs influence the nucleation, growth, and aggregation of crystals by modulating the activity of pro-\/anti-lithogenic proteins, the expression of cell adhesion molecules, and inflammatory pathways. Consequently, therapeutic strategies targeting PTMs may offer novel avenues for the prevention and management of kidney stones. Future research should focus on integrating multi-omics approaches with functional validation to elucidate the dynamic regulatory networks of PTMs within the stone microenvironment, thereby advancing the development of precision medicine.<\/jats:p>","DOI":"10.3390\/cells15060554","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T15:38:01Z","timestamp":1773934681000},"page":"554","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Role of Protein Post-Translational Modifications in the Pathogenesis of Nephrolithiasis: Mechanistic Insights and Translational Potential"],"prefix":"10.3390","volume":"15","author":[{"given":"Wenlong","family":"Wan","sequence":"first","affiliation":[{"name":"Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baokang","family":"Wang","sequence":"additional","affiliation":[{"name":"Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyi","family":"Yang","sequence":"additional","affiliation":[{"name":"Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xun","sequence":"additional","affiliation":[{"name":"Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Yu","sequence":"additional","affiliation":[{"name":"Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/s41581-025-00990-x","article-title":"Kidney stone disease: Risk factors, pathophysiology and management","volume":"21","author":"Bargagli","year":"2025","journal-title":"Nat. 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