Laura De Rosa1,3, Elena Enzo2,3, Michele Palamenghi2,3, Laura Sercia2,3 and Michele De Luca2 1Holostem Terapie Avanzate, S.r.l., 41125 Modena, Italy 2Centre for Regenerative Medicine “Stefano Ferrari,” University of Modena and Reggio Emilia, 41125 Modena, Italy Correspondence: michele.delucaunimore.it

↵3 These authors contributed equally to this work.

Epidermolysis bullosa (EB) is a devastating genetic skin disease typified by a plethora of different phenotypes and ranking from severe, early lethal, to mild localized forms. Although there is no cure for EB, recent progress in pharmacology and molecular and cellular biology is boosting the development of new advanced therapeutic strategies. Here we will focus on two main categories of such therapies: (1) those aimed at controlling inflammation and inducing reepithelialization of the wounds, and (2) those, perhaps more challenging and ambitious, that aim to permanently regenerate a fully functional epidermis, which requires targeting of epidermal stem cells. In both cases, the genetic variants underlying the different EB forms and factors, such as genetic background, modifier genes, comorbidities, and lifestyle, all of which impinge on EB genotype–phenotype correlation, need to be defined.