Cmya5, also known as cardiomyopathy-associated 5, is a striated muscle protein. It belongs to the TRIM superfamily and is involved in cardiac excitation-contraction coupling. Specifically, it plays a crucial role in establishing the architecture and positioning of cardiac dyads, which are essential microdomains formed by the apposition of transverse tubules and junctional sarcoplasmic reticulum near Z-lines. It may also be involved in protein kinase A signalling and vesicular trafficking based on identified interactions [3].

In CMYA5-ablated mice, dyad architecture, dyad positioning at Z-lines, and junctional sarcoplasmic reticulum Ca2+ release are disrupted, leading to cardiac dysfunction and an inability to tolerate pressure overload. This demonstrates that CMYA5 anchors the junctional sarcoplasmic reticulum to Z-lines, regulates dyad Ca2+ release, and is vital for normal cardiac function [1]. Also, in Fhl2-targeted knockout mouse hearts or in a humanised mouse model of hypertrophic cardiomyopathy with reduced FHL2 expression, CMYA5 redistributes into the perinuclear and intercalated disc region, indicating an interaction between FHL2 and CMYA5 that impacts CMYA5's subcellular compartmentation [2].

In conclusion, CMYA5 is essential for cardiac dyad formation and function. Research using gene knockout mouse models has revealed its role in maintaining normal cardiac function, and disruption of CMYA5 can lead to cardiac diseases. Additionally, its interaction with other proteins like FHL2 shows its involvement in subcellular compartment regulation, contributing to our understanding of cardiac biology and disease mechanisms.