ARCN1 encodes archain 1, the delta subunit of the COPI (coat protein complex I) coatomer, a cytosolic protein complex essential for vesicular trafficking 1. The protein functions as a core component of COPI-coated vesicles, mediating retrograde Golgi-to-ER transport of dilysine-tagged proteins and anterograde ER-to-Golgi biosynthetic transport 2. ARCN1 recognizes dilysine motifs and associates reversibly with Golgi membranes in an ARF-dependent manner, maintaining Golgi structural integrity and regulating protein processing and endocytic recycling 3. Beyond classical vesicular trafficking, ARCN1 has emerged as a key regulator of innate immunity and viral infection. ARCN1 suppresses anti-RSV immune responses by promoting STUB1-mediated degradation of IKKε, an essential kinase for type I interferon production 4. Similarly, miR-33a inhibits influenza A virus replication partly by downregulating ARCN1 expression, indicating the protein's importance in viral trafficking 5. Clinically, ARCN1 mutations cause a rare syndromic disorder characterized by intrauterine growth restriction, micrognathia, short stature, developmental delay (71.4% of patients), microcephaly, and genitourinary malformations 6. Severe manifestations include hepatoblastoma, cataracts, and lethal skeletal abnormalities, with phenotype severity correlating with COPI trafficking dysfunction and ER stress responses 3. This constellation defines ARCN1-related syndrome, a disorder spanning from embryonic lethality to milder presentations.