Compartmentalization of protein kinases with substrates is a mechanism that may promote specificity of intracellular phosphorylation events. We have cloned a low‐molecular weight A‐k inase A nchoring P rotein, called AKAP18, which targets the cAMP‐dependent protein kinase (PKA) to the plasma membrane, and permits functional coupling to the L‐type calcium channel. Membrane anchoring is mediated by the first 10 amino acids of AKAP18, and involves residues Gly1, Cys4 and Cys5 which are lipid‐modified through myristoylation and dual palmitoylation, respectively. Transient transfection of AKAP18 into HEK‐293 cells expressing the cardiac L‐type Ca 2+ channel promoted a 34 9% increase in cAMP‐responsive Ca 2+ currents. In contrast, a targeting‐deficient mutant of AKAP18 had no effect on Ca 2+ currents in response to the application of a cAMP analog. Further studies demonstrate that AKAP18 facilitates GLP‐1‐mediated insulin secretion in a pancreatic β cell line (RINm5F), suggesting that membrane anchoring of the kinase participates in physiologically relevant cAMP‐responsive events that may involve ion channel activation.