TACC3 (transforming acidic coiled-coil containing protein 3) is a microtubule-associated protein essential for mitotic spindle organization and chromosome 4. Primary function: TACC3 regulates centrosome-mediated nuclear migration and serves as a component of the TACC3/ch-TOG/clathrin complex that stabilizes kinetochore fibers and maintains kinetochore fiber tension during mitosis 12. In human oocytes, TACC3 is a critical component of the human oocyte microtubule organizing center (huoMTOC), required for proper meiotic spindle assembly and oocyte maturation 3. Mechanism: TACC3 localizes to mitotic spindle poles and functions as an inter-microtubule bridge. The protein participates in spindle checkpoint activation and regulates cell cycle progression through metaphase/anaphase transition. Disease relevance: TACC3 is implicated in multiple cancers through oncogenic gene fusions and altered expression. FGFR3-TACC3 fusions occur in urothelial bladder carcinoma 4 and glioblastoma 5, with the fusion protein displaying constitutive kinase activity that induces chr4 segregation defects and aneuploidy. TACC3 overexpression correlates with resistance to targeted therapies in HER2-positive breast cancer and hepatocellular carcinoma, where it suppresses immunogenic cell death 67. Clinical significance: Genetic variants at the FGFR3/TACC3 locus (4p16.3) are associated with bladder cancer susceptibility, with stronger effects in women 8. TACC3 inhibition restores therapeutic response to T-DM1 in resistant breast cancer and enhances anti-PD-1 immunotherapy efficacy in hepatocellular carcinoma, suggesting TACC3 as a therapeutic target 67.