Because disrupting Rpgrip1l resulted in consistent changes in the desmogleins under both in vivo and in vitro conditions, and the blistering phenotype observed in Rpgrip1l–/–skins is similar to what is seen in pemphigus, a severe blistering disorder caused primarily by the disruption of the desmogleins, we focused our investigation on the desmogleins. This evidence concerns the gene RPGRIP1L and pemphigus.