Protein Hook homolog 3

HOOK3 (Protein Hook homolog 3) is an adapter protein that links the dynein motor complex to cellular cargos and enhances dynein processivity by facilitating interaction with dynactin, enabling sustained microtubule-based transport (UniProt: Q86VS8). It functions as a component of the FHF complex, which promotes vesicle trafficking, Golgi architecture, and AP-4 complex distribution. The protein also participates in endosomal receptor clearance and is targeted by bacterial virulence factors during infection.

HOOK3 is predominantly involved in intracellular trafficking and microtubule motor function. No canonical disease associations are documented in UniProt for this protein.

In Alzheimer's Disease, HOOK3 shows reduced expression in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics; mean log2FC = −0.54), indicating downregulation across the analyzed subcellular fractions. This decrease may reflect impaired axonal transport or vesicular trafficking capacity in AD pathophysiology, consistent with the known role of dynein dysfunction in neurodegenerative disease, though the functional consequence of reduced HOOK3 levels in AD progression requires further investigation.