COPZ2 encodes the zeta 2 subunit of the coat protein complex I (COPI), which mediates intracellular protein transport. As a component of the coatomer complex, COPZ2 participates in COPI vesicle coat formation and is essential for retrograde Golgi-to-endoplasmic reticulum transport of dilysine-tagged proteins 1. The zeta subunit may regulate coat assembly kinetics through its association-dissociation properties with the COPI complex, influencing biosynthetic protein transport rates. Clinically, COPZ2 dysfunction has implications for multiple diseases. In hematopoiesis, mutations in the related COPZ1 gene cause severe congenital neutropenia by disrupting retrograde protein transport and impairing granulocytic differentiation through JAK/STAT and HIF1α pathway dysregulation; notably, COPZ2 transduction rescued this defect 2. In cancer biology, COPZ2 is downregulated in most tumor cell lines, and its loss renders tumors dependent on COPZ1 for survival; COPZ2 harbors tumor-suppressive microRNA-152, providing a therapeutic opportunity for selective tumor cell killing 1. Reduced COPZ2 expression correlates with unfavorable prognosis in thyroid cancer 3 and hepatocellular carcinoma 4, and COPZ2 appears as a candidate driver gene in triple-negative breast cancer 5. Additionally, genetic variants regulating COPZ2 expression associate with Alzheimer's disease susceptibility 6.