RBM20 cardiomyopathy is a severe and arrhythmogenic form of DCM caused by pathogenic variants in the cardiac splicing factor RBM20. In FP-1, we investigated the role of the RBM20 target CAMK2D, and the role of LMNA phosphorylation in the development of the disease. We discovered that RBM20 cardiomyopathy is driven by excessive CAMK2D activation, and we could inhibit development and progression of disease by CAMK2D inhibition (Figure 1). Furthermore, even though we found no evidence of a critical role for LMNA phosphorylation in RBM20 cardiomyopathy, we did uncover a novel role of phosphorylated LMNA in RNA splicing. These results led to new questions, that will be addressed in FP-2, where we will merge with A06.
