8.A.23.3.1
TMEM25 of 366 aas and up to 4 TMSs, scattered throughout the protein (N-terminal, C-terminal and at residues ~150 and 250. The expression of  Tmem25 is strongly influenced by glutamate ionotropic receptor kainate type subunit 4, and it is primarily localized to late endosomes in neurons (Zhang et al. 2019). The effects of TMEM25 on neuronal excitability are likely mediated by N-methyl-D-aspartate receptors. TMEM25 affects the expression of the NR2B subunit and interacts with NR2B; both colocalize to late endosome compartments. TMEM25 induces acidification changes in lysosome compartments and accelerates the degradation of NR2B, and TMEM25 expression is decreased in brain tissues from patients with epilepsy and epileptic mice. TMEM25 overexpression attenuated the behavioral phenotypes of epileptic seizures, whereas TMEM25 downregulation exerted the opposite effect (Zhang et al. 2019). TMEM25 inhibits monomeric epidermal growth factor receptor (EGFR)-mediated STAT3 activation in the basal state to suppress triple-negative breast cancer progression (Bi et al. 2023).  In neurons, TMEM25 modulates the degradation of the NMDA receptor GRIN2B subunit. Thus, TMEM25 regulates neuronal excitability (An et al. 2023).  TMEM25 is a Par3-binding protein that attenuates claudin assembly during tight junction development (Kamakura et al. 2024).