PRKAR1A encodes the regulatory subunit type 1α of cAMP-dependent protein kinase A (PKA), a critical component of cAMP signaling that modulates serine-threonine kinase activity in response to cAMP levels 1. The protein functions as a negative regulator of PKA catalytic activity, maintaining the inactive PKA holoenzyme state until cAMP binding triggers dissociation and kinase activation 1. Inactivating mutations in PRKAR1A disrupt normal cAMP-PKA signaling, leading to aberrant pathway activation 2. This mechanism underlies Carney complex, an autosomal dominant multiple endocrine neoplasia syndrome characterized by spotty skin pigmentation, cardiac and cutaneous myxomas, and endocrine tumors including primary pigmented nodular adrenocortical disease, pituitary adenomas, thyroid cancers, and gonadal tumors 23. Approximately 70% of Carney complex patients harbor PRKAR1A mutations 3. PRKAR1A mutations also cause acrodysostosis with hormonal resistance, characterized by brachydactyly, facial dysostosis, and impaired hormone responsiveness due to defective cAMP binding 4. Additionally, PRKAR1A loss represents a molecular driver in malignant peripheral nerve sheath tumor progression 5. While PRKAR1A exhibits tumor suppressor properties in affected tissues, it likely functions as a relatively weak tumorigenic signal requiring cooperation with other pathways 6.