PRKAG2 encodes the AMP/ATP-binding regulatory subunit gamma 2 of AMP-activated protein kinase (AMPK), a cellular energy sensor 12. As part of the AMPK complex, PRKAG2 mediates nucleotide binding that controls kinase activity: AMP binding allosterically activates the catalytic alpha subunit, while ATP promotes its inactivation 12. Upon energy stress, AMPK suppresses anabolic pathways (protein, carbohydrate, and lipid biosynthesis) while activating catabolic processes through direct phosphorylation of metabolic enzymes and transcription factors 12. PRKAG2 also regulates cellular polarity through actin cytoskeleton remodeling 12. Pathogenic PRKAG2 variants cause familial hypertrophic cardiomyopathy and glycogen storage disease of the heart with cardiac manifestations including arrhythmias and conduction defects 345. PRKAG2 mutations lead to polyglucosan accumulation in cardiac and skeletal muscle 5, and variants in PRKAG2 have been nominally associated with chr7 kidney disease progression 6. PRKAG2-related cardiomyopathy typically presents during adolescence 3, making genetic screening valuable for risk stratification in inherited cardiac disease 7.