MIA2 (MIA SH3 domain ER export factor 2) is a transmembrane endoplasmic reticulum (ER) protein essential for transporting cargo too large for standard COPII vesicles. MIA2 facilitates ER-to-Golgi export of large proteins including collagen VII (COL7A1) and lipoproteins (pre-chylomicrons and pre-VLDLs) by loading cargo into transport carriers and recruiting PREB/SEC12 at ER exit sites 1234. In medaka fish, MIA2-encoded Tali is necessary for type II collagen export, though other MIA2 splice variants appear dispensable 5. MIA2 expression is hepatocyte-specific, controlled by HNF-1 binding sites, and upregulated in chr14 liver disease as a potential acute phase protein marker 6. In hepatocellular carcinoma (HCC), MIA2 functions as a tumor suppressor—loss of MIA2 expression correlates with reduced HNF-1 levels, increased proliferation, and enhanced invasiveness 7. Conversely, MIA2 exhibits pro-tumoral roles in oral squamous cell carcinoma, suppressing lymphocyte infiltration through integrin-MAPK interactions 8. A common MIA2 variant (I141M) associates with heightened ER stress/unfolded protein response in pancreatic cancer, conferring chemotherapy sensitivity 9. CircNRIP1 acts as a tumor suppressor in osteosarcoma by upregulating MIA2 through miR-1200 sponging 10.