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Updated: May 6, 2026

Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
Published on: January 16, 2016
Unraveling the molecular landscape of kAE1: a narrative review
Priyanka Mungara1, Moubarak Waiss2, Sunny Hartwig3
1Department of Physiology, Membrane Protein Disease Research Group, Faculty of Medicine, College of Health Sciences, University of Alberta, Edmonton, AB, Canada.
Abstract:
Kidney anion exchanger 1 (kAE1) is an isoform of the AE1 protein encoded by the SLC4A1 gene. It is a basolateral membrane protein expressed by α-intercalated cells in the connecting tubules and collecting duct of the kidney. Its main function is to exchange bicarbonate and chloride ions between the blood and urine to maintain blood pH at physiological threshold. The kAE1 protein undergoes multiple post-translational modifications such as phosphorylation and ubiquitination and interacts with many different proteins such as claudin-4 and carbonic anhydrase II. Mutations in the gene may lead to the development of distal renal tubular acidosis, characterized by the failure to acidify the urine, which may result in nephrocalcinosis and in more severe cases, renal failure. In this review, we discuss the structure and function of kAE1, its post-translational modifications, and protein-protein interactions. Finally, we discuss insights gained from the study of kAE1 mutations in humans and in mice.
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