Homer proteins regulate signal transduction, generation of synapses and receptor trafficking. The homer protein family is comprised of three members with each member alternatively spliced to long and short forms. All members of the Homer family are synaptic scaffolding proteins with an N-terminal EVH (Ena/VASP homology 1) and a C-terminal coiled-coil domain. Long forms of the protein contain both EVH1 and coiled-coil domains and are constitutively expressed, whereas the short forms contain only the EVH1 domain and are expressed in an activity dependent manner¹.  

The Homer family includes three members, Homer1b/c, Homer2a/b, and Homer3. Homer2 protein, also called Vesl-2, is a scaffolding protein that is important for the proper organization, localization and signaling of excitatory postsynaptic receptors. Homer2 protein associates with filamentous actin (F-actin) and directly binds to drebrin, an actin-binding and remodeling protein in dendritic spines. The protein also binds to activated Cdc42, a member of the Rho small GTPase family². The protein interacts with mGluR1, mGluR5, PI3 Kinase enhancer (PIKE), inositol 1,4,5-trisphosphate receptors (IP₃), SHANK and other proteins^3,4.

Deletion of the Homer2 gene in mice demonstrates several abnormalities in glutamatergic signaling and in the nucleus accumbens such as reduced basal extracellular glutamate content and reduced function and total protein expression of both mGluR1 and the cystine-glutamate exchanger⁴.