TMED9 is a transmembrane p24 cargo receptor that functions primarily in vesicular protein trafficking within the early secretory pathway 1. It mediates COPI-dependent retrograde transport and coatomer recruitment to early secretory membranes, contributing to p24 complex retention in the cis-Golgi network and ER-Golgi intermediate compartment organization 2. TMED9 self-oligomerizes into higher-order complexes that favor COPI but not COPII recruitment, a structural feature enabling its cargo retention function 2. Mechanistically, TMED9 acts as a quality control receptor that captures misfolded proteins in the early secretory pathway. It associates with misfolded cargo like frameshift-mutant MUC1 and mutant uromodulin, entrapping them in vesicles 13. TMED9 also coordinates clearance of misfolded GPI-anchored proteins via the RESET pathway, facilitating their ER export and Golgi transit for lysosomal degradation 4. Clinically, TMED9 dysregulation contributes to proteinopathies and cancer. Small molecule inhibitor BRD4780 binding to TMED9 rescues toxic protein accumulation in mucin 1 kidney disease and autosomal dominant tubulointerstitial kidney disease, reducing ER stress and kidney damage in patient organoids and mice 13. TMED9 is overexpressed in glioblastoma and epithelial ovarian cancer, correlating with poor prognosis and cancer stemness; TMED9 inhibition reduces tumor cell viability and enhances chemotherapy sensitivity 567.