The postsynaptic density protein PSD-95 interacts with the cytoplasmic tail of ion channel subunits via a protein-protein motif called the PDZ domain. PSD-95 belongs to a family of PDZ domain-containing proteins that includes SAP97/Dlg, PSD-93/chapsyn-110, and SAP102. These proteins are characterized by three PDZ domains in the N-terminal half and an SH3 and guanylate kinase-like domain in the C-terminal region. They may be involved in the localization and clustering of ion channels and receptors at synaptic sites. Other PDZ domain-containing proteins such as glutamate receptor interacting protein (GRIP), Homer, and multi-PDZ-domain protein (MUPP1) do not contain guanylate kinase-like domains, but have also been implicated in receptor localization. MUPP1 contains thirteen PDZ domains and is expressed in human heart, brain, placenta, liver, skeletal muscle, kidney, and pancreas. In addition, smaller variants of MUPP1 are expressed in heart, liver, kidney, and brain. The C-terminal region of the 5-HT2c receptor interacts with MUPP1, suggesting that MUPP1 may have important protein-protein interactions during G-protein coupled receptor signaling.