In cardiac muscle, Cadherin-2 is an integral component in adherens junctions residing at intercalated discs, which function to mechanically and electrically couple adjacent cardiomyocytes.

[11][12][13] Cadherin-2 plays a role in development as a calcium dependent cell–cell adhesion glycoprotein that functions during gastrulation and is required for establishment of left-right asymmetry.

[18][19] In cardiac muscle, Cadherin-2 is found at intercalated disc structures which provide end-on cell–cell connections that facilitate mechanical and electrical coupling between adjacent cardiomyocytes.

Mice with altered expression of N-cadherin and/or E-cadherin showed a dilated cardiomyopathy phenotype, likely due to malfunction of intercalated discs.

[27] In agreement with this, mice with ablation of N-cadherin in adult hearts via a cardiac-specific tamoxifen-inducible Cre N-cadherin transgene showed disrupted assembly of intercalated discs, dilated cardiomyopathy, impaired cardiac function, decreased sarcomere length, increased Z-line thickness, decreases in connexin 43, and a loss in muscular tension.

These animals showed a prolonged action potential duration, reduced density of inward rectifier potassium channel and decreased expression of Kv1.5, KCNE2 and cortactin combined with disrupted actin cytoskeleton at the sarcolemma.

In human dilated cardiomyopathy, it was shown that Cadherin-2 expression was enhanced and arranged in a disarrayed fashion, suggesting that disorganization of Cadherin-2 protein in heart disease may be a component of remodeling.