At least two pathways have been linked to cardiac desmosomal protein homeostasis, one which is resident (CSN6) to the desmosome and one found in the cytosol (calpain); however, future studies should focus on how these pathways work cooperatively to degrade desmosomal proteins in the context of human ARVC-associated desmosomal mutations. The gene discussed is COPS6; the disease is Arrhythmogenic right ventricular dysplasia.