The membrane-bound adenylyl cyclases (ACs) represent one of the major families of effector enzymes for G protein-coupled receptors. Eight human AC isoforms (AC1 through AC4), encoded by separate genes, have been identified up to now. Most of the adenylate cyclase genes are comprised of 11-26 exons and distributed over a q6-430 kb. The majority of the adenylate cyclases previously described are expressed discretely in defined peripheral tissues, the type 4 adenylate cyclase (AC4) is apparently expressed in a variety of peripheral tissues and in the central nervous system, mainly in olfactory system. AC5 proteins are localized on photoreceptor cells and are also designated as GC1 and GC2. The AC5 protein resembles the other adenylyl cyclases in its predicted and proposed structure. AC5 resembles the type 6 (AC6) adenylyl cyclase in its amino acid sequence but becomes divergent at N and C-terminal ends. The AC5 and AC6 proteins are co-localized in most of the visual organs (photoreceptor cells) and are associated with other protein complexes. Both AC5 and AC6 enzymes play an important role in synaptic plasticity by coordinating overlapping synaptic inputs from Gs and Gi coupled receptor stimulation.