COPG2 encodes the gamma-2 subunit of coatomer protein complex I (COPI), a cytosolic complex essential for vesicular transport between the endoplasmic reticulum and Golgi apparatus. COPG2 functions as a component of non-clathrin-coated vesicles that mediate biosynthetic protein transport and retrograde Golgi-to-ER transport of dilysine-tagged proteins [UniProt]. The complex requires ARF proteins for membrane recruitment and influences Golgi structural integrity and LDL receptor recycling [UniProt]. Genomically, COPG2 is located on chromosome 7 within an imprinted domain. While some studies report partial imprinting in mouse tissues, human COPG2 demonstrates predominantly biallelic expression in fetal tissues and adult lymphocytes, thus escaping genomic imprinting despite residing adjacent to the paternally imprinted MEST gene 1. Notably, COPG2 expression is downregulated in human cortex compared to other primates, suggesting a role in human brain development 2. Tissue-specific alternative polyadenylation at the MEST locus can regulate allelic usage at COPG2 in the developing central nervous system through transcriptional interference 3. Clinically, COPG2 has emerged as relevant to Alzheimer's disease, where genome-wide association analysis identified COPG2 as significantly associated with the amyloid-β42/Aβ40 ratio in case-only analyses 4. Despite its chr7 location within an autism susceptibility region (7q32), mutation screening and association studies provided no evidence for an etiological role in autism 5.