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Significance The etiology of heart disorders remains poorly understood. In this paper, we show for the first time to our knowledge, that protein palmitoylation plays a critical role in heart structure and function. We demonstrate that Aph2 (Ablphilin 2) is a palmitoyl transferase and identify phospholamban, a cardiomyopathy disease gene, as a substrate. Some of the heart defects of anAph2 −/− mouse can be rescued by phospholamban ablation. In addition, the present study reveals critical roles for protein palmitoylation in embryonic/postnatal survival and eye development.

Palmitoyl acyltransferase Aph2 in cardiac function and the development of cardiomyopathy