family of proteins that contain the PDZ domain. This sequence of amino-acids is found in many thousands of known proteins. PDZ domain proteins are widespread in eukaryotes and eubacteria, whereas there are very few examples of the protein in archaea. PDZ domains are often associated with other protein domains and these combinations allow them to carry out their specific functions. Three of the most well documented PDZ proteins are PSD-95, GRIP, and HOMER. PSD-95 is a brain synaptic protein with three PDZ domains, each with unique properties and structures that allow PSD-95 to function in many ways. In general, the first two PDZ domains interact with receptors and the third interacts with cytoskeleton-related proteins. The main receptors associated with PSD-95 are NMDA receptors. The first two PDZ domains of PSD-95 bind to the C-terminus of NMDA receptors and anchor them in the membrane at the point of neurotransmitter release. The first two PDZ domains can also interact in a similar fashion with Shaker-type K+ channels. A PDZ interaction between PSD-95, nNOS and syntrophin is mediated by the second PDZ domain. The third and final PDZ domain links to cysteine-rich PDZ-binding protein (CRIPT), which allows PSD-95 to associate with the cytoskeleton. Glutamate receptor interacting protein (GRIP) is a post-synaptic protein that interacts with AMPA receptors in a fashion analogous to PSD-95 interactions with NMDA receptors. When researchers noticed apparent structural homology between the C-termini of AMPA receptors and NMDA receptors, they attempted to determine if a similar PDZ interaction was occurring. A yeast two-hybrid system helped them discover that out of GRIP's seven PDZ domains, two (domains four and five) were essential for binding of GRIP to the AMPA subunit called GluR2. This interaction is vital for proper localization of AMPA receptors, which play a large part in memory storage. Other researchers discovered that domains six and seven of GRIP are responsible for connecting GRIP to a family of receptor tyrosine kinases called ephrin receptors, which are important signaling proteins. A clinical study concluded that Fraser syndrome, an autosomal recessive syndrome that can cause severe deformations, can be caused by a simple mutation in GRIP. HOMER differs significantly from many known PDZ proteins, including GRIP and PSD-95. Instead of mediating receptors near ion channels, as is the case with GRIP and PSD-95, HOMER is involved in metabotropic glutamate signaling. Another unique aspect of HOMER is that it only contains a single