Gna12, encoding the G protein subunit α 12, is a G-protein α subunit that plays diverse roles in biological processes. It is involved in signaling pathways such as the C5aR1-PLCβ2-PI3K-AKT-ERK1/2 signaling pathway, and is associated with various physiological and pathological conditions including inflammatory bowel disease, ovarian cancer, liver injury, preeclampsia, and normal pressure hydrocephalus [1,2,3,4,6]. Genetic models, like gene knockout (KO) models, can be used to study its functions.

In macrophages, Gna12 deficiency enhances C5a-induced migration by upregulating the C5aR1-PLCβ2-PI3K-AKT-ERK1/2 signaling, suggesting it acts as an anti-inflammatory factor [1]. In hepatocytes, Gα12 overexpression by endoplasmic reticulum (ER) stress exacerbates acute liver injury via ROCK1-mediated dysregulation of ALOX12 and miR-15a, while Gα12-deficient animals and cells show less severe acetaminophen-induced lipid peroxide-induced ferroptosis [3]. In muscle stem cells (MuSCs), inactivation of Gna12-Gna13 completely abrogates MuSC quiescence, which depletes the MuSC pool and is associated with accelerated sarcopenia during aging, indicating Gna12-Gna13 signaling is crucial for MuSC quiescence [5].

In conclusion, Gna12 is a multifunctional gene involved in regulating cell migration, cell viability, and stem cell quiescence. Its role in diseases such as liver injury and sarcopenia, as revealed through KO models, provides valuable insights into the underlying molecular mechanisms, which may help develop therapeutic strategies for these conditions.