Recent in vitro and in vivo data have demonstrated that cystatin C plays protective roles via pathways that are dependent on inhibition of cysteine proteases, such as cathepsin B, or by induction of autophagy42 and protects neuronal cells against mutant copper-zinc superoxide dismutase-mediated toxicity.43 Our data suggest that the increase in CST1 expression in response to AF treatment induces autophagy as a chemotherapy-resistant mechanism. Here, CST3 is linked to atrial fibrillation.