Consistent with an interchangeable function between KCTD1 and KCTD15 in keratinocytes, neither K14Cre+Kctd1fl/fl mice nor K14Cre+Kctd15fl/fl mice showed an apparent skin or hair phenotype, whereas inactivation of both Kctd1 and Kctd15 in keratinocytes (K14Cre+Kctd1fl/flKctd15fl/fl mice) resulted in skin and hair abnormalities that phenocopied the sparse hair and anhidrosis clinical findings in SEN syndrome patients with KCTD1 mutations. The gene discussed is KCTD15; the disease is anhidrosis.