{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T14:43:53Z","timestamp":1777128233641,"version":"3.51.4"},"reference-count":108,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"INSERM","award":["ANR-17-CE14-0040-Pheno2Geno"],"award-info":[{"award-number":["ANR-17-CE14-0040-Pheno2Geno"]}]},{"name":"ANR","award":["ANR-17-CE14-0040-Pheno2Geno"],"award-info":[{"award-number":["ANR-17-CE14-0040-Pheno2Geno"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mutations in NKCC2 generate antenatal Bartter syndrome type 1 (type 1 BS), a life-threatening salt-losing nephropathy characterized by arterial hypotension, as well as electrolyte abnormalities. In contrast to the genetic inactivation of NKCC2, inappropriate increased NKCC2 activity has been associated with salt-sensitive hypertension. Given the importance of NKCC2 in salt-sensitive hypertension and the pathophysiology of prenatal BS, studying the molecular regulation of this Na-K-2Cl cotransporter has attracted great interest. Therefore, several studies have addressed various aspects of NKCC2 regulation, such as phosphorylation and post-Golgi trafficking. However, the regulation of this cotransporter at the pre-Golgi level remained unknown for years. Similar to several transmembrane proteins, export from the ER appears to be the rate-limiting step in the cotransporter\u2019s maturation and trafficking to the plasma membrane. The most compelling evidence comes from patients with type 5 BS, the most severe form of prenatal BS, in whom NKCC2 is not detectable in the apical membrane of thick ascending limb (TAL) cells due to ER retention and ER-associated degradation (ERAD) mechanisms. In addition, type 1 BS is one of the diseases linked to ERAD pathways. In recent years, several molecular determinants of NKCC2 export from the ER and protein quality control have been identified. The aim of this review is therefore to summarize recent data regarding the protein quality control of NKCC2 and to discuss their potential implications in BS and blood pressure regulation.<\/jats:p>","DOI":"10.3390\/cells13100818","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T03:35:55Z","timestamp":1715744155000},"page":"818","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Protein Quality Control of NKCC2 in Bartter Syndrome and Blood Pressure Regulation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2167-5766","authenticated-orcid":false,"given":"Kamel","family":"Laghmani","sequence":"first","affiliation":[{"name":"Centre de Recherche des Cordeliers, INSERM, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, F-75006 Paris, France"},{"name":"CNRS, ERL8228, F-75006 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1152\/physrev.00011.2004","article-title":"Molecular physiology and pathophysiology of electroneutral cation-chloride cotransporters","volume":"85","author":"Gamba","year":"2005","journal-title":"Physiol. 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