Prkag2 encodes the γ2 regulatory subunit of 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK), an enzyme that modulates glucose uptake and glycolysis. It plays a crucial role in cardiac metabolism [2,4,5]. Mutations in Prkag2 can lead to glycogen storage diseases and cardiac syndromes, highlighting its importance in maintaining normal physiological functions [1,2,4,5].

Mutations in Prkag2 are associated with PRKAG2 syndrome, an autosomal-dominant disorder. This syndrome is characterized by ventricular pre-excitation, cardiac hypertrophy, and progressive conduction system degeneration [1,2,3,4]. The syndrome is also associated with glycogen accumulation in heart tissue, presenting as hypertrophic cardiomyopathy [1]. There are cases where novel Prkag2 variants have been found in patients with liver cirrhosis, expanding the mutational spectrum [1]. Additionally, infants with Prkag2 mutations may mimic Pompe disease, emphasizing the need for confirmatory testing [5].

In conclusion, Prkag2 is essential for normal cardiac metabolism and its mutations are linked to various cardiac and metabolic disorders. The study of Prkag2-related syndromes, especially through the identification of novel mutations, helps in understanding the complex interplay between metabolism and cardiac function, and may potentially guide better diagnostic and treatment strategies for these rare genetic diseases.