COPZ1 encodes the zeta-1 subunit of the coatomer protein complex I (COPI), which mediates intracellular vesicular transport between the endoplasmic reticulum and Golgi apparatus 1. The protein is essential for retrograde protein transport from the Golgi to the ER and plays a critical role in maintaining cellular homeostasis 1. COPZ1 functions as a non-oncogene addiction factor in multiple cancer types, where tumor cells become selectively dependent on its activity due to silencing of the paralogous gene COPZ2 2. Loss-of-function mutations in COPZ1 cause severe congenital neutropenia by disrupting granulocytic differentiation and activating interferon signaling pathways 1. In cancer contexts, COPZ1 depletion triggers multiple cell death mechanisms including ferroptosis through NCOA4-mediated iron dysregulation 3, abortive autophagy, ER stress, and immunogenic cell death with type I interferon activation 4. COPZ1 is overexpressed across various tumor types and correlates with poor prognosis 5. The protein serves as a therapeutic target, as its inhibition selectively kills tumor cells while sparing normal cells that retain COPZ2 expression 2. COPZ1 also facilitates viral replication by mediating transport of viral proteins to replication sites 6.