TMED2, a member of the transmembrane emp24 domain (TMED) family, is essential for the transport of cargo proteins between the endoplasmic reticulum (ER) and Golgi [7]. It is involved in multiple biological processes such as the formation of plasma membrane lipid nanodomains, regulation of Hedgehog (HH) signaling, and is important for normal morphogenesis of mouse embryos and placenta [1,2,7]. It also plays roles in innate immune responses to DNA viruses by potentiating MITA signaling [9].

In cancer research, TMED2 has been extensively studied. In breast cancer, it is overexpressed and associated with poor prognosis, and it can induce cisplatin resistance via the KEAP1-Nrf2 pathway [3]. In epithelial ovarian cancer, silencing TMED2 decreased cell proliferation, migration, and invasion in vitro and inhibited ovarian cancer growth in mice, as it activates the IGF2/IGF1R/PI3K/Akt pathway [4]. In glioma, TMED2 is essential for cell proliferation, migration, invasion, and tumor formation in mouse models, by enhancing EGFR-AKT signaling through facilitating EGFR recycling [5]. In multiple myeloma cell lines, downregulating TMED2 expression decreased cell viability, altered the cell cycle, and increased apoptosis [8]. In head and neck squamous carcinoma, TMED2 serves as a biomarker for poor prognosis [6].

In conclusion, TMED2 is crucial for protein transport between the ER and Golgi and has far-reaching impacts on various biological processes. Its role in multiple cancer types, as revealed through in vitro and in vivo studies including mouse models, makes it a potential therapeutic target for these malignancies.