HOOK1 is a microtubule-tethering protein that functions as a component of the FHF complex, which promotes vesicle trafficking and AP-4 complex distribution to the perinuclear region 1. HOOK1 acts as a dynein activating adaptor, enhancing stability of the dynein-dynactin motor complex and mediating cargo-specific interactions with signaling endosomes 2. At the molecular level, HOOK1 regulates endosomal sorting of clathrin-independent cargo proteins like CD98 and CD147 into recycling endosomes through interactions regulated by γ-taxilin 3. Clinically, HOOK1 exhibits tumor-suppressive functions across multiple cancer types. In esophageal squamous cell carcinoma, HOOK1 induces necroptosis and inhibits cell proliferation and migration, serving as a prognostic biomarker 4. In renal cell carcinoma, HOOK1 suppresses tumor growth and metastasis via TGF-β pathway regulation and TNFSF13B degradation; the HOOK1 agonist meletin shows enhanced antitumor activity when combined with sunitinib or nivolumab 5. In ovarian cancer, HOOK1 maintains cancer stem cell properties through protein homeostasis regulation; HOOK1 downregulation increases endoplasmic reticulum stress and reduces stemness 6. Additionally, HOOK1 expression correlates with obesity-related traits, showing depot-specific expression in visceral adipose tissue 7.