Transmembrane protein 65 (TMEM65)

Transmembrane protein 65 (TMEM65) is a mitochondrial inner membrane protein essential for maintaining normal mitochondrial function, especially mitochondrial respiratory chain activity[1][2]. TMEM65 is also present in the cardiac intercalated disc and is necessary for proper cardiac conduction by facilitating the localization of key proteins such as connexin 43 and the sodium channel NaV1.5 to the intercalated disc[3][5][7]. In cardiomyocytes, TMEM65 physically interacts with the sodium channel β1 subunit, and its loss leads to altered cardiac conduction, dilated cardiomyopathy, and heart failure[3][5]. Recent functional analyses provide evidence that TMEM65 acts as the mitochondrial Na^+/Ca^2+ exchanger, forming homodimers critical for ion exchange and mitochondrial bioenergetics[6]. In oncology, TMEM65 is frequently amplified and overexpressed in gastric cancer, promoting cell proliferation, invasion, and resistance to apoptosis through activation of the PI3K-Akt-mTOR pathway, and serves as an independent prognostic biomarker[1]. Pathogenic mutations in TMEM65 are linked to severe mitochondrial encephalomyopathy with neurological and cardiac deficits[1]. No approved drugs or inhibitors of TMEM65 are currently known, but its multifaceted roles in mitochondrial function, cardiac physiology, and cancer suggest it may be a potential therapeutic target under investigation.

Other names

TMEM65transmembrane protein 65TMM65_HUMAN