Tmem168, a protein-coding gene, comprises 697 amino acid residues with some putative transmembrane domains. It has been associated with multiple biological functions and disease-related processes. In the nucleus accumbens (NAcc), it is involved in regulating methamphetamine dependence, and also interacts with osteopontin, potentially influencing dopaminergic function. Additionally, it may play a role in the Wnt/β-catenin pathway in glioblastoma cells [1,3,4].

In mouse models, overexpression of Tmem168 in the NAcc of mice (NAc-TMEM mice) attenuated methamphetamine-induced hyperlocomotion and place preference, and suppressed methamphetamine-induced extracellular dopamine elevation [3]. Heterozygous Tmem168 1616G>A knock-in mice showed ventricular tachyarrhythmias and conduction disorders upon pharmacological stimulation, due to a decrease in Na+ current and Nav 1.5 protein expression in ventricular cardiomyocytes [2]. In glioblastoma cells, knockdown of Tmem168 via siRNA prevented cell viability, induced cell cycle arrest, and promoted apoptosis by blocking the Wnt/β-catenin pathway [4].

In conclusion, Tmem168 plays crucial roles in drug-related behaviors, cardiac arrhythmogenesis, and glioblastoma cell proliferation. The use of mouse models, such as gene-modified mice, has significantly contributed to understanding its functions in these disease-relevant biological processes, offering potential therapeutic targets for methamphetamine dependence, Brugada syndrome, and glioblastoma.