Hook2 is a dynein adaptor protein that plays crucial roles in multiple cellular processes. It promotes the assembly of the dynein-dynactin motor complex, which is involved in microtubule-based transport. Hook2 is associated with pathways related to mitosis, ciliogenesis, polarized cell migration, and aggresome formation, thus being of great biological importance. Genetic models, such as KO mouse models, can be valuable for studying its functions [1-5].

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

In ciliogenesis, Hook2 localizes at the Golgi apparatus and centrosome/basal body in human retinal epithelial cells. Its depletion disrupts ciliogenesis before ciliary vesicle formation. Hook2 interacts with and stabilizes pericentriolar material protein 1 (PCM1), and together with Rab8a, regulates a limiting step in ciliogenesis [2].

Regarding polarized cell migration, Hook2 is an interactor for the aPKC/PAR6α complex, localizing this complex at the centrosome. Depletion of Hook2 decreases PAR6α at the centrosome during cell migration [3].

Overexpression of Hook2 promotes the accumulation of the cystic fibrosis transmembrane regulator in aggresomes, while a dominant-negative form inhibits aggresome formation, suggesting it contributes to the pericentrosomal localization of aggresomes [4]. Hook2 localizes to the centrosome throughout the cell cycle, binds directly to centriolin/CEP110, and its function is necessary for the radial organization of microtubules and microtubule regrowth after depolymerization [5].

In conclusion, Hook2 is essential for processes like mitotic progression, cytokinesis, ciliogenesis, polarized cell migration, and aggresome formation. Studies using KO or other loss-of-function models have revealed its specific roles in these biological processes. While not directly tied to diseases in the provided content, understanding its functions can potentially shed light on underlying mechanisms related to cell-cycle-associated and ciliopathy-related diseases in the future.