An additional difference between the MHS condition and the stress of heart failure reported to unleash calpain cleavage of JPh2 is that the cardiac condition is accompanied by structural remodeling with loss of couplons and reduction in JPh2 content (Wu et al., 2014; Zhang et al., 2013), while no structural remodeling has been reported in muscle of MHS patients. Here, JPH2 is linked to heart failure.