PLN and cardiomyopathy: Abnormal perinuclear localization of PLN has been identified as a hallmark of PLN-R14del cardiomyopathy, and we have recently demonstrated that this abnormality is associated with structurally altered SR.9 Cardiomyocytes with these abnormal SR structures eventually undergo necrosis, leading to replacement fibrosis.9 Treatment with ASO resulted in a dose-dependent reduction of perinuclear PLN staining, with other SR markers also returning to normal localization post-treatment.