The variants contribute to the EBS phenotype through two distinct mechanisms: direct keratin abnormalities due to pathogenic variants in the <i>Krt14</i> gene, and indirect effects via pathogenic mutation in the <i>KLHL24</i> gene, which interfere with the natural proteasome-mediated degradation pathway of KRT14. This evidence concerns the gene KLHL24 and epidermolysis bullosa simplex.