Prkaa1, also known as AMPKα1, is the α -subunit of 5 -AMP -activated protein kinase. It serves as a major cellular sensor of energy and nutrients, regulating various metabolic pathways such as glycolysis, fatty acid oxidation, and autophagy [2,4,5]. It is involved in crucial biological processes like erythrocyte maturation, immune cell regulation, and is associated with diseases including gastric cancer and metabolic syndrome [1,2,4]. Genetic models, especially knockout (KO) mouse models, are valuable for studying its functions.

In KO mouse models, endothelial-specific Prkaa1 knockout alleviated high-fat diet (HFD)-induced metabolic syndromes, suggesting its role in promoting HFD-induced inflammation [2]. In Prkaa1-deficient myeloid cells, genes for glucose and lipid metabolism were downregulated, and macrophage recruitment and viability were suppressed, reducing the development of diet-induced metabolic disorders [5]. In the context of fluoride-induced developmental neurotoxicity, NaF-treated models showed that regulating Prkaa1-activated PINK1/Parkin-dependent mitophagy could be a potential treatment [3].

In conclusion, Prkaa1 is essential for regulating metabolism, immune responses, and cellular homeostasis. Gene knockout mouse models have been instrumental in revealing its role in metabolic syndrome, fluoride-induced neurotoxicity, and other disease-related processes, providing insights into potential therapeutic strategies for these conditions.