Finally, we present evidence that three human genes encoding CEP-290-dependent TZ components, TMEM17, TMEM138, and TMEM231, are mutated in Oral-Facial-Digital type 6 (OFD6) syndrome families; furthermore, a novel mammalian TZ protein we uncovered, Tmem80, represents an excellent ciliopathy candidate. Here, TMEM17 is linked to ciliopathy.