PRKAB2 encodes the beta-2 non-catalytic subunit of AMP-activated protein kinase (AMPK), a key energy sensor that regulates cellular metabolism. As a scaffold protein, PRKAB2 bridges the alpha and gamma subunits to assemble the functional AMPK complex 1. The gene exhibits isoform-specific functions distinct from PRKAB1, with PRKAB2 showing broader transcriptional impact and being essential for mesoderm specification and cardiac differentiation in human pluripotent stem cells 1. PRKAB2 demonstrates clinical relevance across multiple diseases. In pediatric adrenocortical tumors, lower PRKAB2 expression correlates with poor prognosis including relapse, metastasis, and reduced survival rates, serving as an independent prognostic factor 2. Copy number variations in PRKAB2 are associated with congenital heart defects, particularly tetralogy of Fallot 3. The gene shows pharmacogenetic significance in diabetes treatment, with variants affecting metformin response 4. Additionally, PRKAB2 expression is altered in inflammatory conditions, with decreased levels observed in dermatitis patients and differential methylation patterns in hyperuricemia 56. These findings highlight PRKAB2's critical role in metabolic regulation, cardiac development, and disease susceptibility.