Tmem138, encoding a putative transmembrane protein, is associated with ciliopathies and plays a crucial role in ciliary function. It is localized to the ciliary transition zone, which is essential for molecular trafficking in cilia and is structurally analogous to the photoreceptor connecting cilium (CC) [1,2]. This gene is potentially involved in pathways related to protein trafficking across the photoreceptor CC, and its study using genetic models can help understand ciliary-related biological processes.

Genetically inactivating mouse Tmem138 (using a KO mouse model) abolished outer segment (OS) morphogenesis in photoreceptors, followed by rapid photoreceptor degeneration [1]. Tmem138 was found localized to the photoreceptor CC and was required for the localization of Ahi1 to the distal subdomain of the CC. Rhodopsin, an OS protein, was mislocalized throughout the mutant cell body prior to OS morphogenesis. Ablation of Tmem138 in mature rods recapitulated the molecular changes in germline mutants, causing failure of disc renewal and disintegration of the OS. Tmem138 also interacts reciprocally with rhodopsin and Tmem231, and the ciliary localization of Tmem231 was altered in mutant photoreceptors [1].

In conclusion, Tmem138 is essential for the functional organization of the CC, which is crucial for rhodopsin localization and OS biogenesis in photoreceptors [1]. The study of Tmem138 using KO mouse models has provided insights into the mechanisms underlying ciliopathies, specifically those related to photoreceptor function and retinal dystrophies.