TMEM138 is a transmembrane protein essential for ciliogenesis and cilium assembly 1. Mechanistically, TMEM138 localizes to the ciliary transition zone and connecting cilium, where it is required for proper organization of this molecular gate 2. Specifically, TMEM138 facilitates localization of Ahi1 to the distal subdomain of the connecting cilium and is critical for rhodopsin trafficking and outer segment biogenesis in photoreceptors 2. TMEM138 interacts reciprocally with rhodopsin and related protein Tmem231, and its loss causes mislocalization of these proteins and photoreceptor degeneration 2. At the molecular level, TMEM138 localizes to the transition zone in a CEP-290-dependent manner as part of a distinct module separate from core MKS or NPHP components 3. Clinically, TMEM138 mutations are associated with Joubert syndrome 16, a rare autosomal recessive disorder characterized by cerebellar vermis hypoplasia and developmental delay 4. TMEM138 mutations have also been identified in oral-facial-digital syndrome cases, expanding its ciliopathy disease associations 5. Additionally, TMEM138 variants associate with skin pigmentation in African populations, suggesting pleiotropic functions 6 7. Compound mutations in TMEM138 combined with mutations in other ciliary genes can produce severe clinical phenotypes 8.