PRKAR2A encodes the regulatory subunit IIα (RIIα) of cAMP-dependent protein kinase (PKA), a critical component of the PKA holoenzyme that regulates cAMP signaling 1. RIIα is a type II regulatory chain that mediates membrane association through binding to anchoring proteins and determines PKA subcellular localization, distinguishing it functionally from other PKA subunits 2. In uterine smooth muscle, PRKAR2A expression is dynamically regulated during pregnancy and labor, with epigenetic control via histone deacetylase activity at GC-rich promoter elements, suggesting a role in maintaining uterine quiescence 1. Loss of PRKAR2A predisposes to hematopoietic malignancies in mice, particularly histiocytic sarcomas and diffuse large B cell lymphomas 3. In fibrolamellar hepatocellular carcinoma, cooperative loss of BAP1 and PRKAR2A causes hepatocyte transdifferentiation into ductal/progenitor-like cells, highlighting its tumor suppressor function 4. PRKAR2A-derived circular RNAs promote colitis-associated colorectal cancer progression through Wnt signaling and serve as biomarkers distinguishing cancer patients 5. In the medial habenula, PRKAR2A deletion decreases hedonic eating and increases exercise motivation by reducing dendritic PKA activity 2. PRKAR2A-AS1 long non-coding RNA is altered in autism spectrum disorder, potentially serving as a diagnostic marker 6. Methylation variations at PRKAR2A are inversely associated with chr3 kidney disease risk 7.