PDZ domains generally associate with both the C-terminus of the receptor and cytoskeletal elements in order to anchor the receptor to the cytoskeleton and keep it in place. Without such an interaction, receptors would diffuse out of the synapse due to the fluid nature of the lipid membrane.

PDZ domains are also utilized to localize elements other than receptor proteins. In the human brain, nitric oxide often acts in the synapse to modify cGMP