Elmod1, short for ELMO domain-containing protein 1, is a guanine nucleoside triphosphatase activating protein (GAP) [1,2,4,5,6]. It acts on the ADP-ribosylation factor (ARF) small GTPase family, especially ARF6, regulating membrane trafficking and cytoskeletal assembly [1,5,6]. This function is crucial for normal development and function in various biological processes, with its study often facilitated by genetic models such as gene knockout mouse models.

In rda/rda mice lacking functional Elmod1, utricle hair cell cuticular plates initially form normally but degenerate after postnatal day 5, accompanied by abnormal hair bundle development, including apical membrane detachment, stereocilia elongation and fusion, and altered membrane trafficking [1]. These phenotypes suggest that Elmod1-mediated conversion of ARF6 to its GDP-bound form is necessary for stabilizing hair bundle and apical membrane structures [1]. Deletion of Elmod1 in cells also leads to decreased ability to form primary cilia, loss of some ciliary proteins, and abnormal protein accumulation at the Golgi, indicating its role in ciliogenesis and ciliary protein traffic [2]. In humans, a novel mutation in Elmod1 has been associated with mental retardation and autism spectrum disorder, demonstrating differences in phenotypes compared to mouse models [3].

In conclusion, Elmod1 is essential for the stabilization of apical structures in hair cells and regulation of ciliogenesis and ciliary protein traffic. The study of Elmod1 knockout mouse models has provided insights into its role in these biological processes and its potential association with human diseases such as mental retardation and autism spectrum disorder [1,2,3].