Transmembrane emp24 domain-containing protein 9 (TMED9)

Transmembrane emp24 domain-containing protein 9 (TMED9) is a member of the p24 (TMED) family of cargo receptors localized mainly on the endoplasmic reticulum (ER), ER-Golgi intermediate compartment (ERGIC), and post-Golgi vesicles. TMED9 forms oligomeric complexes with other p24 family members and is essential for normal vesicular trafficking between the ER and the Golgi, as well as for quality control of misfolded proteins such as misfolded GPI-anchored proteins. It plays roles in autophagy, lysosomal sorting, the unconventional secretion of proteins during ER stress, and in the trafficking of certain viral proteins, such as the SARS-CoV-2 spike protein. TMED9 is implicated as an oncoprotein in several cancers (e.g., glioblastoma, ovarian, hepatocellular, and breast cancer), where its upregulation correlates with poor prognosis, tumor cell migration, and stemness. Recent work has identified the small molecule BRD4780 as a TMED9 inhibitor that impedes tumorigenic functions in glioma and induces ER retention of misfolded protein cargo[1][2][3][4][6].

Other names

GP25L2p24alpha2p24a2GMP25Glycoprotein 25L2p24 family protein alpha-2p25HSGP25L2Gtransmembrane p24 trafficking protein 9transmembrane emp24 protein transport domain containing 9

Inhibition of protein trafficking and secretory pathway (BRD4780 blocks ER export of misfolded GPI-anchored proteins by interfering with TMED9 localization/function), Possible enhancement of anti-tumor effect when combined with standard chemotherapeutics