The human body is built up of millions of cells that together function as tissues and organs. Desmosomes are tiny structures on cell surfaces that enable cells not only to stick to their neighbours but also to communicate with them. Desmosomes in skin cells have been studied in detail partly because this organ is the most easily accessible to researchers. Also, mutations (mistakes) in the genes that code for the various protein components of desmosomes can cause serious life‐long skin problems such as blistering, fragility or excessive skin thickness. Some mutations affect desmosomes in the heart, causing life‐threatening problems such as sudden disturbance in heart rhythm. In this paper, researchers at a major UK dermatology centre review current knowledge of the desmosomal genes, proteins and diseases. Using clear diagrams, they summarize the roles of the three protein superfamilies involved: the cadherins (desmogleins and desmocollins); the armadillo proteins (plakoglobin plakophilin); and the plakin family (desmoplakin). Genetic disorders affecting the skin or mucous membranes (which line and protect, for example, the mouth, stomach and lungs) can be caused by mutations in any one of nine genes (DSG1, DSG3, DSC2, DSC3, JUP, PKP1, DSP, CDSN, PERP); hair disorders can result from mutations in eight genes (DSG4, DSC2, DSC3, JUP, PKP1, DSP, CDSN, PERP); mutations in three genes can cause syndromes affecting skin, hair and heart (DSC2, JUP, DSP) and mutations in five genes can cause heart problems without any abnormality in the skin or hair (DSG2, DSC2, JUP, PKP2, DSP). This knowledge will help dermatologists to advise patients with desmosomal skin and hair disorders. Linked Article: Lee and McGrath. Br J Dermatol 2021; 184:596–605. Linked Article: Lee and McGrath. Br J Dermatol 2021; 184:596–605. [ABSTRACT FROM AUTHOR]