PRKACB encodes the catalytic subunit beta of cAMP-dependent protein kinase (PKA), a key mediator of G-protein coupled receptor signaling. It transduces cAMP-dependent signals to regulate diverse cellular processes including cell proliferation, differentiation, microtubule dynamics, and ion flux 12. PRKACB phosphorylates multiple substrates including RPTOR to suppress mTORC1 signaling 3 and GPKOW to modulate RNA binding 4. The protein contains redox-sensitive cysteine residues (Cys200, Cys344) that enable PKA to function as an oxidative stress sensor, initiating RNF25-dependent E-cadherin degradation in hepatocellular carcinoma metastasis 5. PRKACB is predominantly expressed in brain tissue with neuroprotective functions against neurodegeneration 67. Clinically, PRKACB alterations are associated with multiple malignancies: fusion genes involving PRKACB occur in extrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma 89, and drive intraductal oncocytic papillary neoplasm morphology 10. Pathogenic PRKACB variants also contribute to Carney complex (characterized by myxomas and endocrine tumors) and adrenal Cushing syndrome 1112.