Defining a Unifying Mechanism for Select Cariomyopathy-Linked Variants of Desmoplakin

Arrhythmogenic cardiomyopathy (ACM) is a disease that affects 1 in 2000 Americans every year and segregates with sudden cardiac death (SCD). ACM is linked to genetic variants in desmosomal genes, however the molecular mechanisms by which desmosomal variants result in ACM remain unclear. Our novel results in human heart explants identify that desmoplakin (DSP), a desmosomal gene product, is cleaved via a calpain-dependent mechanism. To define a...