Cmya5, also known as cardiomyopathy-associated 5, is a muscle-specific member of the TRIM superfamily [3]. It is essential for cardiac excitation-contraction coupling as it plays a key role in establishing the architecture and positioning of cardiac dyads, the microdomains formed by the apposition of transverse tubules and junctional sarcoplasmic reticulum adjacent to Z-lines [1]. This function is crucial for normal cardiac function and is likely involved in pathways related to muscle contraction and calcium ion regulation.

In CMYA5-ablated mouse models, dyad architecture and positioning at Z-lines are disrupted, along with junctional sarcoplasmic reticulum Ca2+ release, leading to cardiac dysfunction and inability to tolerate pressure overload [1]. This indicates that CMYA5 anchors junctional sarcoplasmic reticulum to Z-lines, regulating dyad Ca2+ release, and its absence has severe consequences for cardiac function. Additionally, in Fhl2-targeted knockout mouse hearts or a humanized mouse model of hypertrophic cardiomyopathy with reduced FHL2 expression, CMYA5 redistributes into the perinuclear and intercalated disc region, suggesting an interaction between FHL2 and CMYA5 that impacts CMYA5's subcellular compartmentation [2].

In conclusion, CMYA5 is vital for maintaining proper cardiac dyad architecture and function, which is essential for normal heart function. The findings from CMYA5-related gene knockout mouse models have provided insights into its role in cardiac diseases, highlighting its significance in understanding cardiomyopathy pathogenesis [1,2].