In this study, we leverage a large collection of human RV tissues from explanted DCM and ischemic (ICM) hearts, stratified with either pRV or RVF, and from nonfailing (NF) hearts from human donors, in order to identify a robust reactivation of the fetal noncanonical WNT receptor ROR2, upregulation of ROR2/Ca2+ responsive protease calpain-μ, and increased cleavage of calpain-target cytoskeletal proteins specifically in severe RVF (27–29). Here, FZD1 is linked to familial dilated cardiomyopathy.