Desmocollin-2/3 (DSC2/3) are transmembrane proteins belonging to the calcium-dependent cadherin superfamily and are essential components of desmosomes, which are intercellular junctions that provide structural integrity to epithelial tissues. These proteins mediate cell-cell adhesion through homophilic and heterophilic interactions with other desmosomal cadherins, such as desmogleins. DSC2/3 play crucial roles in maintaining tissue cohesion, especially in mechanically stressed environments. Abnormal expression or dysfunction of DSC2/3 has been implicated in various diseases, including skin blistering disorders like pemphigus and arrhythmogenic cardiomyopathy. In cancer, DSC2/3 can have dual roles, acting as tumor suppressors or promoters depending on the context. For example, DSC2 is downregulated in many cancers, such as hepatocellular carcinoma and gastric cancer, where it inhibits cell proliferation and promotes apoptosis. Conversely, in some cancers like pancreatic cancer, loss of DSC2/3 may lead to increased cell migration and metastasis.