Physiological Functions of Nedd4-2: Lessons from Knockout Mouse Models
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Updated: Feb 7, 2026

Assessment of Kidney Function in Mouse Models of Glomerular Disease
Published on: June 30, 2018
Jantina A Manning1, Sharad Kumar1
1Centre for Cancer Biology, University of South Australia and SA Pathology, GPO Box 2471, Adelaide, SA 5001, Australia.
Abstract:
Protein modification by ubiquitination plays a key evolutionarily conserved role in regulating membrane proteins. Nedd4-2, a ubiquitin ligase, targets membrane proteins such as ion channels and transporters for ubiquitination. This Nedd4-2-mediated ubiquitination provides a crucial step in controlling the membrane availability of these proteins, thus affecting their signaling and physiological outcomes. In one well-studied example, Nedd4-2 fine-tunes the physiological function of the epithelial sodium channel (ENaC), thus modulating Na+ reabsorption by epithelia to maintain whole-body Na+ homeostasis. This review summarizes the key signaling pathways regulated by Nedd4-2 and the possible implications of such regulation in various pathologies.
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