ERG1 activators that disrupt inactivation can dramatically shorten the action potential duration in cardiomyocytes (Bentzen et al., 2011; Zhang H. et al., 2012; Yu et al., 2016; Perry et al., 2019; Qile et al., 2019), but are associated with an unexpected increased incidence of arrhythmia in vivo (Bentzen et al., 2011). The gene discussed is KCNH2; the disease is cardiac arrhythmia.