Underscoring the importance of this regulatory circuit for human biology, mutations in TCOF1 account for ~90% of cases of the craniofacial disease Treacher Collins Syndrome (The Treacher Collins Syndrome Colla, 1996; Jones et al., 2008), while additional transcription factor binding sites in the promoter of KBTBD8 drive melanoma, a cancer of neural crest origin (Hayward et al., 2017). The gene discussed is KBTBD8; the disease is Treacher-Collins syndrome.