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THEM4, also known as CTMP, binds specifically to the carboxy-terminal regulatory domain of PKB/Akt at the plasma membrane and acts as a negative regulator, reversing the phenotype of v-Akt-transformed cells. Hypermethylation of the THEM4 promoter and transcriptional downregulation of the gene has been reported in multiple glioblastomas, suggesting that epigenetic regulation of THEM4 may play a role in the progression of this cancer. Bioinformatic analysis, confirmed by in vitro testing, indicates that THEM4 is a broad-range, high activity acyl-CoA thioesterase. Recent reports have also indicated that TMEM4 is a mitochondrial protein whose overexpression is associated with an increase in mitochondrial membrane depolarization and caspase-3 and PARP cleavage, suggesting that THEM4 is involved in the apoptotic program. The additional higher molecular weight bands seen in the immunoblot may represent post-translationally modified TMEM4.