Gain-of-Function Mutation in Ubiquitin-Ligase KLHL24 Causes Desmin Degradation and Dilatation in hiPSC-Derived Engineered Heart Tissues

Dynamically loaded engineered heart tissues (dyn-EHTs) were generated from human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes from two patients and three (non)familial controls. KLHL24 RNA interference or direct desmin overexpression recovered desmin protein levels, restoring morphology and function in patient-derived dyn-EHTs.