Tmed7, short for transmembrane emp24 domain-containing protein 7, is a COPII adaptor protein. It functions as a cargo sorting adaptor in the early secretory pathway, facilitating the anterograde transport of proteins from the endoplasmic reticulum to the Golgi. It is involved in the regulation of innate immunity, especially in Toll-like receptor 4 (TLR4)-mediated inflammatory signaling pathways, and is also associated with sperm maturation and embryo development [2,3,6]. Genetic models are valuable for studying Tmed7 as they can help clarify its precise functions in these processes.

In innate immunity, TMED7 is required for the trafficking of TLR4 from the endoplasmic reticulum to the cell surface. Depletion of TMED7 reduces TLR4 signaling mediated by the adaptor protein MyD88 [4]. RHBDL4, an intramembrane protease, triggers the degradation of TMED7, counteracting TLR4 transport to the cell surface. TLR4 activation also mediates transcriptional upregulation of RHBDL4, forming a negative feedback loop. In a mouse model, this mechanism alleviates septic shock, and a hypomorphic RHBDL4 mutation linked to Kawasaki syndrome further supports the pathophysiological relevance [1]. Overexpression of miR-340-5p, which targets TMED7, can alleviate the injury of A549 cells caused by Mycobacterium tuberculosis infection by inhibiting the activation of NF-κB [5].

In conclusion, Tmed7 plays a crucial role in the regulation of TLR4-mediated inflammatory signaling. Mouse models, especially those related to septic shock and Kawasaki syndrome, have significantly contributed to understanding the role of Tmed7 in disease-related innate immune responses. Its function in protein trafficking also has implications for sperm maturation and embryo development, highlighting its importance in multiple biological processes.