No lysine? No problem: the surprising roles of WNK kinases in physiology and disease.

Overview

Authors: Ji-Ung Jung¹, Ankita B Jaykumar^1,2, Clinton A Taylor IV¹, Melanie H Cobb¹

ORCID iDs: Ji-Ung Jung, Ankita B Jaykumar, Clinton A Taylor IV, Melanie H Cobb

Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, U.S.A
Department of Pharmaceutical Sciences, University of North Texas Health, Fort Worth, TX 76107, U.S.A

Institutions: The University of Texas Southwestern Medical Center (United States); University of North Texas (United States); University of North Texas Health Science Center (United States)

Journal: The Biochemical journal, volume 483, issue 11, pages 2139-2161

Dates: received 21 April 2026; accepted 2 October 2026; published online 19 October 2026; in print November 2026

Type: Review · Language: English

License: CC BY

Identifiers: DOI 10.1042/bcj20250110 · PMID 42894500 · PMCID PMC13686953 · OpenAlex W7222919807

Open access: hybrid, a free copy (OpenAlex)

Status: data only (how the code is found and verified)

Categories: human (organism), other condition (population), cellular / molecular (subfield)

Keywords: brain, cancer, kinase, metabolic regulation, transport, WNK

MeSH: Protein Serine-Threonine Kinases*, Animals, Humans, Ion Transport, Minor Histocompatibility Antigens, Neoplasms, Signal Transduction, WNK Lysine-Deficient Protein Kinase 1 (* major topic)

Topic: Ion Transport and Channel Regulation (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex

Funding: Welch Foundation (The Welch Foundation) (I1243); HHS | National Institutes of Health (NIH) (K99AG075161, R01 HL147661); HHS | NIH | National Cancer Institute (NCI) (P30CA142543)

Citations: not cited yet (Europe PMC); 240 references in the paper

Abstract

WNK (With No lysine K) protein kinases gained early attention because gain-of-function mutations in genes encoding two of them cause hypertension. They differ from other kinases due to the unusual location of the catalytic lysine, hence the name WNK. These kinases control many aspects of ion transport in the kidney and are essential for development and maintenance of the cardiovascular system. In the present review, we describe WNK proteins and selected substrates, in particular, the kinases oxidative stress-responsive kinase 1 and SPS1-related proline/alanine-rich kinase, and their regulation. We spotlight findings that emphasize the broad relevance of WNKs in normal physiology and disease. Our overview focuses on basic aspects of ion transport that occur in many cell types and tissues, functions in the endothelial system, interactions with insulin-dependent and metabolic pathways, the importance in the brain in part through controlling chloride ion balance, and the whirlwind of findings in cancer that reveal how WNK signaling can be repurposed. Other actions that may be of equal importance, e.g., influences on the immune system, are touched on only briefly. We also note a few genome-wide association studies that have uncovered multiple SNPs in genes encoding WNKs and downstream effectors in an array of diseases, in anticipation of more to come in the future.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data and to no code of its authors: see the Data section.

Tracing map

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Data

Datasets cited

rcsb.org/structure/1atp, at PDB; found in the text, “WNK structure and isoforms”
rcsb.org/structure/2erk, at PDB; found in the text, “WNK structure and isoforms”
rcsb.org/structure/3dak, at PDB; found in the text, “WNK structure and isoforms”
rcsb.org/structure/42qa, at PDB; found in the text, “WNK structure and isoforms”
rcsb.org/structure/5d9h, at PDB; found in the text, “WNK structure and isoforms”

Versions

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Version 1, 1 November 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 4 authors, 6 keywords, 8 MeSH terms, 3 funders, 239 references.

Cite

This paper

Jung, J.-U., Jaykumar, A. B., Taylor, C. A., & Cobb, M. H. (2026). No lysine? No problem: the surprising roles of WNK kinases in physiology and disease. The Biochemical journal, 483(11), 2139-2161. https://doi.org/10.1042/bcj20250110

BibTeX

@article{jung2026no, author = {Jung, Ji-Ung and Jaykumar, Ankita B and Taylor, Clinton A and Cobb, Melanie H}, title = {{No lysine? No problem: the surprising roles of WNK kinases in physiology and disease}}, journal = {The Biochemical journal}, year = {2026}, month = nov, volume = {483}, number = {11}, pages = {2139--2161}, publisher = {Portland Press}, issn = {0264-6021}, doi = {10.1042/bcj20250110}, url = {https://doi.org/10.1042/bcj20250110}, pmid = {42894500}, pmcid = {PMC13686953} }

RIS

TY - JOUR AU - Jung, Ji-Ung AU - Jaykumar, Ankita B AU - Taylor, Clinton A AU - Cobb, Melanie H TI - No lysine? No problem: the surprising roles of WNK kinases in physiology and disease T2 - The Biochemical journal J2 - Biochem J PY - 2026 DA - 2026/11/01 VL - 483 IS - 11 SP - 2139 EP - 2161 SN - 0264-6021 PB - Portland Press DO - 10.1042/bcj20250110 UR - https://doi.org/10.1042/bcj20250110 LA - en ER -

CSL-JSON

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