Highlights of this review paper "Physiological Functions of Nedd4-2: Lessons from Knockout Mouse Models" Trends in Biochemical Sciences  Vol 43, Issue 8, August 2018, Pages 635-647.

  • Nedd4-2 (also called NEDD4L) is a HECT-type ubiquitin ligase that is involved in the regulation of multiple membrane proteins.
  • Nedd4-2 is likely to influence multiple signaling networks via specific targeting of proteins in different tissues, and variants in human NEDD4L are associated with developmental disorders, hypertension, and end-stage renal disorders.
  • Mouse knockout studies indicate that Nedd4-2 is a key regulator of Na+ homeostasis, and ENaC is one of its most important physiological substrates.
  • Pathological consequences of dysregulated Nedd4-2 in mice include disorders of the respiratory, renal, cardiac, neural, and immune systems.
  • Observation that Nedd4-2 deficiency causes kidney disease provides a link between dysregulated Na+ reabsorption and renal tubular injury.