Tmem117, Transmembrane protein 117, is located in the endoplasmic reticulum and plasma membrane. It may be involved in multiple biological processes including mitochondrial function regulation, as it can modulate mitochondrial membrane potential and is thus associated with oxidative stress regulation [2,4,5]. It also seems to be related to pathways like the unfolded protein response during ER stress [3].

In male mice, Tmem117 inactivation in vasopressin magnocellular neurons of the hypothalamus increases hypoglycemia-induced vasopressin secretion, leading to higher glucagon secretion, and this effect is estrus cycle-phase dependent in female mice. This shows its role as a physiological regulator of glucagon secretion in the counterregulatory response to hypoglycemia [1]. In cardiac-specific Tmem117-knockout mice, Tmem117 deficiency attenuated angiotensin II-induced cardiac hypertrophy, alleviated oxidative stress and endoplasmic reticulum stress, and mitigated mitochondrial injury, indicating that down-regulation of Tmem117 may be a new therapeutic strategy for preventing and treating cardiac hypertrophy [2].

In conclusion, Tmem117 is involved in the regulation of mitochondrial function, glucagon secretion in response to hypoglycemia, and the development of cardiac hypertrophy. The gene knockout mouse models have provided insights into its role in hypoglycemia response and cardiac disease, suggesting its potential as a therapeutic target in these areas.