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patients with PPP, several exceptions have been reported, suggesting the existence of modifier mutations. M€ ossner et al. sought to investigate these issues through the analysis of an extended disease cohort including 61 patients with GPP, 258 with PPP and four with ACH. The study, which is published in this issue of the BJD, confirmed the presence of substantial genetic heterogeneity. This was especially marked in PPP, where > 90% of cases were mutation negative. While this figure is slightly lower in other surveys, there is no doubt that further gene identification studies will be required to illuminate the genetic landscape of PPP and improve its molecular diagnosis. Given the evidence for genetic heterogeneity, this will require rigorous phenotyping of patients and the use of standardized diagnostic criteria such as those devised by the European Rare And Severe Psoriasis Expert Network (ERASPEN). Another important aspect of the study carried out by M€ ossner et al. is the thorough analysis of 11 individuals harbouring a single IL36RN mutation. It showed that none of these patients carried an exon deletion or duplication alongside the identified missense mutation. This strongly suggests the presence of modifier alleles at other loci. Indeed, the authors identified two unrelated patients with mutations in both IL36RN and AP1S3. A similar finding was recently reported by Mahil et al., indicating that digenic inheritance is an important feature of pustular psoriasis. Of note, the observation that AP1S3 alleles can modify the effects of IL36RN defects allowed Mahil et al. to demonstrate a role for AP1S3 in the regulation of IL-36 signalling. Thus the identification of further modifier alleles will improve our understanding of the intricate pathways that lead to the onset of pustular psoriasis.