TMEM43, also known as LUMA, is a transmembrane protein encoded by a highly conserved gene and widely expressed across species [2]. It has been implicated in various biological processes and diseases. TMEM43 is associated with pathways related to cardiac function, metabolism, and cancer development, and its study via genetic models can provide insights into its functions.

In mouse models, TMEM43 knockdown in hearts deteriorated LPS-induced cardiac injury and dysfunction, while overexpression alleviated these effects, suggesting it protects against sepsis-induced cardiac injury by inhibiting ferroptosis [1]. The Ser358Leu mutation of TMEM43 in mice led to hyper-activated nuclear factor κB (NF-κB) activation, driving the expression of pro-fibrotic gene TGFβ1, and enhancing downstream signals in arrhythmogenic right ventricular dysplasia/cardiomyopathy [3]. Additionally, Tmem43 S358L mutant mice displayed systolic dysfunction, arrhythmias, fibro-fatty infiltration in the heart, and abnormal intestinal phenotypes, with disrupted WNT-β-catenin and PPARG signaling [4].

In conclusion, TMEM43 plays a crucial role in maintaining cardiac and metabolic homeostasis. Mouse models, especially those with TMEM43 knockout or specific mutations, have revealed its significance in sepsis-induced cardiac injury and arrhythmogenic cardiomyopathy. These findings enhance our understanding of related disease mechanisms and may provide potential therapeutic targets.