The present invention provides compositions and methods useful in the diagnosis and prognosis of Carney complex (CNC), as well as methods and compositions for the identification of compounds useful in the treatment and/or prevention of CNC. In addition, the present invention provides compositions and methods useful in the diagnosis and treatment of conditions associated with skin pigmentation defects, including but not limited to freckling, as well as endocrine tumors including, but not limited to adrenal and pituitary tumors. In addition, the present invention provides methods and compositions for the diagnosis and treatment of various types of cancers associated with abnormal activity of protein kinase A. In particular, the present invention provides genetic and other sequence information, as well as assay systems that will find use in these and related areas.