TPM1 and dilated cardiomyopathy: While TPM1 mutations are predominantly reported in hypertrophic (HCM) and dilated cardiomyopathy (DCM)—attributed to sarcomeric hypercontractility (HCM) or actin destabilization (DCM) (Perry, 2001; Halder et al., 2024)—and while the E181K mutant was shown to cause hypercontractility in vitro by (Gupte et al., 2015), our study in a clinical RCM context reveals that its unique pathogenicity is mediated specifically through calcium-CaMKII-HDAC4 signaling axis disruption.