Pck2, also known as mitochondrial phosphoenolpyruvate carboxykinase, is an enzyme involved in multiple biological processes. It participates in gluconeogenesis, especially in glucose - deprived conditions. It also has non - enzymatic roles and is associated with pathways like mitochondrial respiration, redox balance, and phospholipid remodeling. Pck2 is crucial for maintaining cellular homeostasis and its study using genetic models can provide insights into various physiological and pathological states [2,5].

In multiple disease - related studies, Pck2 has shown significant impacts. In tumor - repopulating cells, down - regulation of Pck2 confers ferroptosis resistance, while higher levels of Pck2 and its phosphorylated target are correlated with better response to chemo - and radiotherapy in nasopharyngeal carcinoma [1]. In non - small cell lung cancer, depletion or inhibition of Pck2 enhances the efficacy of gefitinib by inducing ferroptosis [4]. In endothelial cells, Pck2 silencing perturbs proteostasis, leading to cell demise and impaired vessel sprouting [2]. In intestinal antibody - secreting cells, loss of Pck2 exacerbates colitis due to increased oxidative stress [3]. In vascular smooth muscle cells, PCK2 knockdown attenuates proliferation via the Akt - FoxO - PCK2 pathway, and Pck2 knockout mice show attenuated neointimal hyperplasia [6]. In hepatic ischemia - reperfusion injury, targeting Pck2 can ameliorate hyperlactatemia - mediated ferroptosis [7].

In conclusion, Pck2 plays essential roles in maintaining cellular homeostasis, redox balance, and metabolism. Model - based research, especially gene knockout studies in mice, has revealed its significance in various disease areas such as cancer, colitis, and vascular diseases. Understanding Pck2 provides potential therapeutic targets for these diseases.