Mutations　in　human　ether-a-go-go-related　gene　(hERG)　can　lead　to　type　2　long-QT　syndrome　(LQT2).　The　authors　previously　identified　the　hERG　mutation　G604S　results　in　a　loss　of　function　and　obviously　decreased　current　amplitude　and　impaired　channel　protein　trafficking　when　co-expressed　with　WT-hERG.　The　present　study　further　investigates　the　biological　and　electrophysiological　consequences　of　pharmacologic　chaperones　in　HEK293　cells　expressing　G604S-hERG　or　co-expressing　G604S-hERG　and　WT-hERG.　It　was　found　that　a　low　temperature　(27　degrees　C),　thapsigargin,　NS1643　and　E-4031　fail　to　rescue　the　G604S　mutation.　Interestingly,　only　E-4031　treatment　resulted　in　a　significant　increase　in　hERG　currents　in　cells　co-expressing　G604S-hERG　and　WT-hERG,　correspondingly　more　mature　protein　band　at　155kDa　by　Western　blotting　and　an　increased　membrane　staining　by　confocal　microscopy.　In　addition,　E-4031　treatment　shifted　the　steady-state　half　maximal　activation　voltage　(V-1/2)　of　the　inactivation　curve　by　+8mV　in　cells　co-expressing　G604S-hERG　and　WT-hERG.　The　present　experimental　results　suggest　that　a　G604S　mutation　is　resistant　to　pharmacological　rescue.　E-4031　treatment　resulted　in　a　significant　increase　in　hERG　currents　by　promoting　the　hERG　channel　processing　and　trafficking　in　cells　co-expressing　G604S-hERG　and　WT-hERG.