Prkaca, which encodes the catalytic subunit α of protein kinase A (PKA), is a key player in cAMP-dependent protein kinase signaling. PKA, as a holoenzyme, consists of a regulatory subunit dimer and two catalytic subunits. When cAMP binds to the regulatory subunits, the catalytic subunits are released to phosphorylate downstream targets, thus propagating cAMP-responsive cell signaling events. This signaling pathway is involved in various biological processes, and Prkaca is of great biological importance in maintaining normal physiological functions [7].

In the context of diseases, Prkaca has been implicated in multiple conditions. Somatic mutations in Prkaca are the most frequently altered gene in cortisol-producing adenomas, and patients with these mutations often present with a more severe phenotype at a younger age [3]. Germline Prkaca amplification has been associated with primary pigmented nodular adrenocortical disease (PPNAD), a rare form of ACTH-independent Cushing's syndrome [2]. In fibrolamellar hepatocellular carcinoma, the DNAJB1-Prkaca fusion transcript is the oncogenic driver, and this fusion protein can be a target for peptide-based immunotherapy [1,4]. Also, somatic Prkaca mutations may be related to the accelerated development of aldosterone-and cortisol-producing adenomas during pregnancy [5]. Additionally, Prkaca-related, atrial defects-polydactyly-multiple congenital malformation syndrome is caused by disease-causing variants in Prkaca [6].

In conclusion, Prkaca is essential for cAMP-dependent protein kinase signaling, which is crucial for normal physiological functions. Its involvement in various diseases, such as adrenal tumors, PPNAD, and fibrolamellar hepatocellular carcinoma, has been revealed through studies. Understanding Prkaca's functions in these disease conditions can potentially provide new therapeutic strategies for these diseases.