The MEK-ERK axis plays numerous important roles in the heart, collectively promoting cardiomyocyte survival after injury.(11) Mice lacking ERK1 and ERK2, the exclusive immediate downstream signaling targets of MEK1, display extensive cardiomyocyte apoptosis and enhanced susceptibility to heart failure after chronic pressure overload.(12) As such, the cardiotoxicity of Trm may arise entirely from on-target inhibition of the cardioprotective MEK-ERK axis. Here, MAPK1 is linked to heart failure.