Desmosomes are composed of a number of proteins, including cadherins, armadillo proteins and plakoplilins, which are responsible for mediating cell-cell adhesion. Cadherins are transmembrane proteins that bind to each other on adjacent cells, forming a strong adhesive bond between the cells. In normal tissues, desmosomes help to maintain the structural integrity of the tissue by holding the cells together. During carcinogenesis, the structure and function of desmosomes may be altered. For example, in oral cancer, the expression of certain cadherins may be increased, leading to increased cell-cell adhesion and a more cohesive tumour mass. This may contribute to the ability of cancer cells to evade the immune system and resist chemotherapy. In addition to their role in cell adhesion, desmosomes also play a role in cell signaling. The proteins that make up desmosomes can interact with signaling pathways that regulate cell proliferation, migration and survival. Dysregulation of these pathways may contribute to the development and progression of oral cancer. There is also evidence that desmosomes may be involved in the process of invasion and metastasis, which is the spread of cancer cells from the primary tumour to other parts of the body. Cancer cells that have disrupted or abnormal desmosomes may be more likely to migrate and invade other tissues. Overall, desmosomes appear to be important in the development and progression of oral cancer. Further research is needed to fully understand the role of these cell-cell junctions in the disease and to identify potential therapeutic targets.

Inherited desmosomal diseases are characterised by skin and/or cardiac features. Dermatological features might be a clue in the determination of the underlying life-threatening cardiac disease. This article aims to propose a dermatological algorithm for the diagnosis of desmosomal diseases after a systematic review of published articles. Palmoplantar keratoderma (PPK), hair shaft anomalies and skin fragility are the major features in the 458 patients analysed. Isolated PPK or isolated hair shaft anomalies are associated with a desmosomal disease limited to skin. The combination of PPK and hair shaft anomalies was recorded in 161 patients, and this association is at high risk of cardiac disease (129/161, 80.1%). Skin features had led to cardiac monitoring in only 2.3% of those patients. We delineated three major phenotypes: the PPK-hair shaft anomalies-non-fragile skin subtype (77%), always associated with cardiac involvement; the PPK-hair shaft anomalies-skin fragility-normal cardiac function subtype (19.9%), frequently associated with PKP1 mutations; the PPK-hair shaft anomalies-skin fragility-cardiac involvement subtype (3.1%), always due to DSP mutations. Three mutation hotspots in DSP and JUP account for 90.8% of the patients with cardiac involvement. The combination of PPK and hair shaft anomalies justifies long-term cardiac monitoring.