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Guanylyl Cyclase (GC)-A and GC-B are homologous, cell surface, enzyme receptors that catalyze the formation of the second messenger cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). Atrial natriuretic peptide (ANP) and B-type NP (BNP) bind and activate GC-A, whereas C-type NP (CNP) binds and activates GC-B. GC-A primarily regulates cardiovascular function, which includes decreasing blood pressure, blood volume, and cardiac hypertrophy, but also regulates metabolism, immune function, and hearing. In contrast, GC-B is best known for regulating the female reproductive system and long bone growth, strength, and density. Both GC-A and GC-B contain an extracellular ligand-binding domain, a single membrane-spanning region, and an intracellular region that consists of a kinase homology regulatory domain (KHD), a helix-loop-helix dimerization domain and C-terminal GC …