The key role played by TFIIH is illustrated by the fact that several mutations in its XPB, XPD and TTDA subunits lead to the rare autosomal recessive disorders Xeroderma Pigmentosum (XP), sometimes associated with Cockayne syndrome (XP/CS), and Trichothiodystrophy (TTD). The gene discussed is ERCC2; the disease is Cowden syndrome 1.