Updated project metadata. Desmosomes are multiprotein adhesion complexes that link intermediate filaments to the plasma membrane, ensuring the mechanical integrity of cells across tissues, but how they participate in the wider signalling network to exert their full function is unclear. To investigate this we performed multiplexed proximity biotinylation (BioID). The combined interactomes of the essential desmosomal proteins desmocollin 2a, plakoglobin and plakophilin 2a (Pkp2a) in Madin-Darby canine kidney epithelial cells were mapped and their differences and commonalities characterised as desmosome matured from Ca2+-dependence to the mature, Ca2+-independent, hyper-adhesive state, which predominates in tissues. Results suggest distinct roles of individual desmosomal proteins in linking to cellular signalling pathways that alter substantially when cells change their adhesion state. Moreover, we find support for our dualistic concept of desmosomes in which the properties of Pkp2a differ from those of the other, more stable proteins. The data provide a requisite resource to unravel the nature of desmosomes.