Hook2 is an evolutionarily conserved dynein adaptor protein. It plays essential roles in promoting the assembly of highly processive dynein-dynactin motor complexes, and is involved in multiple crucial cellular processes such as mitotic progression, cytokinesis, ciliogenesis, polarized cell migration, and aggresome formation [1-5]. It is also potentially associated with diseases like primary angle closure glaucoma and type 2 diabetes [5,6,7].

In mitosis, Hook2 binds to and promotes dynein-dynactin assembly. During late G2 phase, it mediates dynein-dynactin localization at the nuclear envelope for centrosome anchoring. It also regulates microtubule nucleation at the centrosome independently of its dynein-binding. Hook2-depleted cells show reduced astral microtubules, spindle positioning defects, and cytokinesis failure [1].

In ciliogenesis, Hook2 localizes at the Golgi apparatus and centrosome/basal body. Its depletion disrupts ciliogenesis before ciliary vesicle formation. It interacts with and stabilizes PCM1, and together with Rab8a, regulates an important step in ciliogenesis [2].

Regarding polarized cell migration, Hook2 is an interactor for the aPKC/PAR6α complex, localizing this complex at the centrosome and regulating centrosome orientation [3]. Overexpression of Hook2 promotes aggresome formation, while a dominant-negative form inhibits it, suggesting it contributes to the pericentrosomal localization of aggresomes [4].

In summary, Hook2 is crucial for various cellular functions including mitosis, ciliogenesis, cell migration, and aggresome formation. Its study, especially through gene-knockout models, helps in understanding the underlying mechanisms of these processes. The potential associations with diseases like glaucoma and type 2 diabetes further highlight its significance in disease-related research, providing insights into possible disease mechanisms and potential therapeutic targets.