Klhl18, Kelch-like protein 18, is a BTB domain-containing protein that binds cullin 3 (CUL3), forming a ubiquitin ligase complex. This complex is involved in multiple biological pathways, such as ubiquitination-mediated protein degradation, which is crucial for maintaining normal cellular functions [2,4].

In Klhl18-deficient mice, several phenotypes have been observed. In rod photoreceptors, Klhl18 -/- mice showed decreased rod light responses and mislocalization of the transducin α-subunit (Tα), indicating that Cul3-Klhl18 ubiquitin ligase modulates rod Tα translocation during light-dark adaptation through ubiquitination of Unc119 [1]. In the inner ear, Klhl18 mutant mice (Klhl18lowf and Klhl18tm1a(KOMP)Wtsi) had progressive, predominantly low-frequency hearing impairment due to inner hair cell dysfunction, suggesting Klhl18 is necessary for maintaining inner hair cell stereocilia and normal function at low frequencies [3]. Depletion of CUL3 and KLHL18 in cells causes a delay in mitotic entry and delayed centrosomal activation of Aurora-A, with KLHL18 promoting Aurora-A ubiquitylation in vivo and in vitro, indicating its role in cell cycle regulation [4].

In summary, Klhl18 plays essential roles in multiple biological processes. Model-based research, especially using Klhl18 KO mouse models, has revealed its significance in light-dark adaptation in the eyes, hearing function in the inner ear, and cell cycle regulation. These findings contribute to understanding the underlying mechanisms of related diseases, such as photoreceptor damage, hearing loss, and potentially cell-cycle-related disorders [1,3,4].