Adenylyl cyclases (ACs) are a family of enzymes that synthesize cAMP, upon stimulation. cAMP is an important second messenger, which regulates carbohydrate, lipid, protein, and nucleic acid metabolism as well as synaptic transmission, ion channel function, and transcription in neurons. There are nine closely related isoforms of ACs (AC1–9) in mammals. All AC isoforms share a primary structure consisting of two hydrophobic regions which comprise six transmembrane helices and three large cytoplasmic domains. The basic catalytic unit of a membrane-bound AC molecule consists of the C1a and C2 domains. The N-terminus domains of ACs are highly variable, and might play a regulatory role.