Prkaca, encoding the catalytic subunit α of protein kinase A (PKA), is a key player in the cAMP signaling pathway. 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 [5]. This process is crucial for various biological functions in all tissues [5].

In diseases, Prkaca has been implicated in multiple conditions. Somatic mutations in Prkaca are the most frequently altered gene in cortisol-producing adenomas, with patients carrying these mutations showing a more severe phenotype and being identified at a younger age [3]. Germline Prkaca amplification has been associated with primary pigmented nodular adrenocortical disease (PPNAD), a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome [2]. Also, the DNAJB1-Prkaca fusion transcript is the oncogenic driver in fibrolamellar hepatocellular carcinoma, and peptide-based immunotherapy targeting this fusion protein has shown efficacy in a single-patient study [1]. Moreover, somatic Prkaca mutations may be correlated with the upregulation of LHCGR, which drives the accelerated growth of co-secretion tumors during pregnancy [4].

In conclusion, Prkaca is essential for cAMP-dependent protein kinase function and cell signaling. Its dysregulation, whether through somatic mutations, germline amplification, or gene fusion, is associated with various adrenocortical and liver-related diseases. Understanding Prkaca's role through research on these disease-associated alterations can potentially lead to new therapeutic strategies for these conditions.