Jph2, encoding junctophilin-2, is an essential gene in cardiomyocytes. It plays crucial roles in calcium handling, maintenance of t-tubule structure, gene transcription, and may regulate mitochondrial function. It is involved in the excitation-contraction (EC) coupling pathway in the heart, which is vital for normal heart performance [2,3].

Rare variants in Jph2 have been associated with a range of cardiac diseases. Autosomal recessive, loss-of-function variants are linked to severe, early-onset dilated cardiomyopathy (DCM), while autosomal dominant missense variants are associated with a wider array of cardiac diseases including hypertrophic cardiomyopathy (HCM), arrhythmia, sudden cardiac death (SCD), and cardiac conduction disease [1]. Jph2 knockout mice exhibit cardiomyocyte mitochondrial swelling and cristae derangements, and Jph2 knockdown in embryonic stem cell-derived cardiomyocytes induces down-regulation of the mitochondrial protein mitofusin-2 (MFN2), disrupting mitochondrial cristae structure and transmembrane potential [3].

In conclusion, Jph2 is essential for normal cardiac function, especially in processes related to calcium handling, t-tubule structure, gene transcription, and mitochondrial function. Studies using Jph2 knockout and knockdown models have revealed its significant role in cardiac diseases, particularly DCM, HCM, arrhythmia, and SCD [1,3].