TMED4

TMED4, or Transmembrane p24 Transporter 4, also known as HNLF, ERS25, or p24a3, plays a role in various cellular processes, including endoplasmic reticulum stress response, heat shock response, apoptosis, and vesicular protein transport, primarily in the early secretory pathway.
The mechanism of action of TMED4 involves the regulation of endoplasmic reticulum stress (ERS) through the IRE1α-XBP1 signaling pathway and NRF2-associated antioxidant responses, promoting the homeostasis of reactive oxygen species (ROS) in regulatory T cells (Tregs), maintaining the expression and suppressive function of Foxp3 in Treg cells. TMED4 is crucial for maintaining the stability and function of Treg cells, and its absence can lead to decreased stability of Foxp3 in Treg cells, affecting their suppressive function, which may consequently result in excessive T cell activation and exacerbated inflammatory responses. TMED4 may also inhibit the proteasomal degradation of IRE1α through the ER-associated degradation (ERAD) system. Dysfunction of TMED4 is associated with various diseases, including Neuronal Ceroid Lipofuscinosis Type 8.