Alterations of Nedd4-2-binding capacity in PY-motif of Na V 1.5 channel underlie Long QT Syndrome and Brugada syndrome.

Our data suggest that the PY-motif plays an essential role in modifying the expression/function of Na 1.5 channels through Nedd4-2-mediated ubiquitination. Alterations of Na 1.5-Nedd4-2 interaction represent a novel pathological mechanism for Na 1.5 channel diseases caused by SCN5A variants.