Indeed, our data highly suggest a fundamental role of the KRT1/10 V2 domain in IH-CM pathogenesis, indicating that the clinical phenotype of a specific keratin disease is not only dependent on the affected keratin or on a specific amino acid change but also relies on changes in defined conformational domains [22, 27] that are responsible for specific functions. The gene discussed is KRT1; the disease is cutaneous mastocytosis.