Transmembrane protein 168 (TMEM168)

Transmembrane protein 168 (TMEM168) is an eleven-pass transmembrane protein predominantly localized to the nuclear membrane. TMEM168 plays a role in regulating cardiac sodium channel (Nav1.5) expression and function via modulation of ubiquitination pathways, maintaining electrical stability in cardiomyocytes, and is implicated in familial Brugada syndrome through pathogenic mutations that disturb protein-protein interactions and sodium current balance[1][3]. In cancer, specifically glioblastoma multiforme, TMEM168 is overexpressed and correlates with poor patient prognosis. Functionally, knockdown of TMEM168 induces cell cycle arrest at G0/G1, decreases cell proliferation, and enhances apoptosis in GBM cells, primarily through suppression of the Wnt/β-catenin signaling pathway[1][2][3][4]. TMEM168 expression may serve as a prognostic biomarker in GBM, and modulating its level affects tumor growth dynamics. Upregulated expression has also been linked to neuropsychiatric disorder-like symptoms in animal models[2]. No currently approved drugs target TMEM168 directly, but its interactions with the Wnt/β-catenin pathway and sodium channels make it a promising therapeutic target and a potential safety concern for cardiac electrophysiology if modulated.

Other names

TMEM168DKFZp564C012FLJ13576transmembrane protein 168

Modulation of Wnt/β-catenin signaling pathway (cell proliferation, apoptosis, cycle regulation); Regulation of ubiquitination and cell-surface expression of sodium channels (Nav1.5) through interaction with E3 ligase Nedd4-2 and αB-crystallin