Cyclic AMP (cAMP) is a common second messenger for a variety of cytokines, hormones, and neurotransmitters. Central to this signaling pathway is the activation of cAMP-dependent protein kinase A (PKA). The non-uniform intracellular distribution of PKA isoforms allows for the delivery of cAMP-transmitted signals to discrete subcellular sites. This is mediated by the attachment of PKA isoforms to the cytoskeleton or organelles by AKAPs. AKAPs simultaneously bind to the RII subunits of PKAII and to the cytoskeleton. At least six AKAP-KL (A kinase anchor proteins expressed in lung and kidney) proteins are generated by alternative mRNA splicing. They are present primarily in lung, kidney, and cerebellum and are absent from many other tissues. All isoforms consists of a 20-residue RII interaction domain. Additionally, AKAP-KL binds and regulates the actin cytoskeleton and exhibits a polarized distribution in situ. Thus, AKAP-KL plays a role in establishing polarity in signaling systems and also functions to focus and amplify cAMP-mediated signals by integrating PKA isoforms with downstream effector molecules.