RYR2 and heart failure: Thus, we suggest that GM1869 is a novel lead candidate for developing multi-targeted drug ligands as proposed previously (Zhang et al, 2023) that may allow further fine-tuning of their effects either towards RyR2 Ca2+ leak or SERCA2a pump activity, respectively, dependent on the pathophysiological context, for example, heart failure affecting ∼2% of the general population with its known hallmarks of RyR2 channel and SERCA2a pump dysfunction (Braunwald, 2015).