Cardiomyopathy-associated protein 5 (CMYA5)

Cardiomyopathy-associated protein 5 (CMYA5), also known as myospryn, is a large, muscle-specific scaffold protein predominantly expressed in striated muscle, particularly cardiomyocytes[1][3][6]. It is a member of the tripartite motif-containing (TRIM) family and contains a SPRY domain. CMYA5 is essential for the organization and stabilization of dyads—specialized nanodomains where the cardiac excitation–contraction machinery operates through coordinated electrical signaling and calcium release for heart muscle contraction[3][5][7]. CMYA5 anchors junctional sarcoplasmic reticulum to Z-lines in the muscle fiber, scaffolds critical proteins (such as titin, α-actinin, desmin, and ryanodine receptor RYR2), and compartmentalizes protein kinase A signaling. Disruption or deficiency of CMYA5 leads to impaired dyad structure, defective calcium handling, and subsequent heart dysfunction, seen in animal models as cardiomyopathy and inability to tolerate cardiac stress[4][5][7]. CMYA5 function or expression may also be associated with neuropsychiatric disease risk, such as schizophrenia[1][4]. Experimental gene therapies using engineered mini-CMYA5 protein show potential in restoring dyad structure and improving outcomes in models of heart failure[2].

Other names

MyosprynC5orf10DTNBP2SPRYD2TRIM76Dystrobrevin-binding protein 2Genethonin-3SPRY domain-containing protein 2Tripartite motif-containing protein 76

Restoration or enhancement of dyad architecture; Improvement of excitation–contraction coupling in failing hearts (via gene therapy expressing truncated CMYA5)