TMEM138 encodes a member of the tetraspanin family of mulit-pass transmembrane proteins. Among various protein networks in primary cilia, proteins of the tectonic complex were found to partly play a role in transporting intracellular vesicles to the cilium. TMEM138 is thought to function as part of this complex by marking post-Golgi vesicles that carry ciliary proteins. TMEM138-tagged vesicles and other transmembrane tagged vesicles are tethered in transport to the base of the cilium, a requirement for ciliary assembly and function. Dysfunctional ciliary genes result in various ciliopathies that arise due to absent or underdeveloped cilia.
TMEM138 dysfunction results in autosomal recessive Joubert Syndrome 16 (JBTS16), a neurodevelopmental and multi-visceral disorder characterized by the Molar Tooth Sign (MTS), a mid-hindbrain malformation easily identifiable through an axial brain MRI scan.