Desmocollin2

Desmocollin-2 (DSC2) is a desmosomal cadherin and a calcium-dependent cell adhesion protein that is a component of desmosomes, structures that provide strong mechanical linkages between neighboring cells. It participates in homophilic adhesion with other Desmocollin-2 molecules and can interact with Desmoglein-2, contributing to the adhesive strength required in tissues subjected to continual stress. The intracellular cytoplasmic tail of DSC2 binds desmosomal plaque proteins such as plakoglobin, plakophilins, and desmoplakin, linking the desmosome to intermediate filaments.

DSC2 is encoded by the DSC2 gene, located on chromosome 18 in humans. The protein is expressed in the heart and various epithelia, reflecting its role in maintaining tissue integrity. Desmocollin-2 is a transmembrane glycoprotein with a large extracellular domain containing cadherin repeats, a single transmembrane segment, and a cytoplasmic tail that anchors the desmosome to the intermediate filament network through plaque proteins.

Functionally, DSC2 contributes to desmosomal cell–cell adhesion that preserves the mechanical cohesion of tissues during contraction and stress. In the heart, it supports cardiomyocyte alignment and synchronized contraction; in epithelia, it participates in barrier function and tissue integrity.

Clinical significance of DSC2 includes associations between pathogenic variants and inherited cardiomyopathies, particularly arrhythmogenic right ventricular cardiomyopathy and dilated cardiomyopathy, often involving ventricular arrhythmias. Most mutations are missense or truncating and disrupt desmosome assembly or function, underscoring the protein’s role in cardiac and epithelial tissue integrity. DSC2 is one member of the desmocollin family, which also includes DSC1 and DSC3, all contributing to desmosomal adhesion.