PRKAR2B encodes the type II-beta regulatory subunit of cAMP-dependent protein kinase A (PKA), a critical component of intracellular signaling 1. As a regulatory subunit, PRKAR2B binds cAMP and mediates PKA activation while facilitating membrane localization through interactions with anchoring proteins 1. PRKAR2B localizes to excitatory post-synapses where it functions as a wake-promoting kinase, competing with sleep-promoting phosphatases (PP1 and calcineurin) to regulate mammalian sleep-wake cycles 2. Dysregulated PRKAR2B expression is implicated in multiple malignancies. In castration-resistant prostate cancer (CRPC), PRKAR2B upregulation promotes metastasis by activating Wnt/β-catenin signaling and inducing epithelial-mesenchymal transition 3. PRKAR2B expression is transcriptionally regulated by the XBP1 transcription factor and suppressed by miR-200b-3p and miR-200c-3p 1. Additionally, PRKAR2B was identified as a hub gene in colorectal liver metastasis development 4 and serves as a target in diabetic kidney disease pathogenesis, where miR-3147-mediated PRKAR2B suppression exacerbates mesangial cell dysfunction 5. In endocrine tissues, PRKAR2B depletion promotes cell proliferation and apoptosis resistance through PKA, MEK/ERK, and NF-κB pathway activation 6. PRKAR2B deficiency also predisposes to hematopoietic malignancies 7. These findings establish PRKAR2B as both a fundamental signaling regulator and an oncogenic driver across multiple disease contexts.