Arrhythmogenic cardiomyopathy (ACM) is a genetic heart disease characterized by fibrofatty replacement of the myocardium, ventricular arrhythmias, heart failure, and an increased risk of sudden cardiac death. Diagnosis is challenging and once established, genetic diagnosis can only be achieved in 60% of ACM patients. Even for patients with an identified pathogenic variant, the molecular mechanisms underlying the disease are poorly understood and characterized. Currently, there is no curative treatment available. To address these issues, we aim to uncover novel causal and modifier genes that could serve as potential therapeutic targets. We anticipate gaining new pathomechanistic insights in ACM and possibly in other inherited cardiac arrhythmias (ICAs). Furthermore, the incorporation of the identified genes in gene panels will enhance diagnostic accuracy and family screening. Lastly, it will guide the development of novel drugs or the repurposing of FDA/EMA-approved drugs.