The HOMER protein family includes Homer1, 2, and 3. These proteins are mainly expressed in the neuronal post-synaptic density (PSD) where they play a role in post-synaptic signaling and receptor trafficking by forming multivalent links with various receptors and PSD scaffolding proteins. The expression level of Homer proteins in non-neural tissues is very low in comparison with that in the nervous system, HOMER3 also expressed in the lung, spleen, kidney and ovary. In the mouse brain HOMER3 is concentrated in the dendritic spines of Purkinje cells connecting the parallel fibers and is also present in their axons, In the hippocampus, HOMER3 is concentrated in the CA2-CA3 regions^1,2.

All three proteins in the HOMER family have several isoforms as a result of alternative splicing, HOMER3 are shown to exist in both long and short forms, the latter without the C-terminal coiled-coil domains. HOMER3 mRNA is subject to alternative splicing at five different sites giving rise to ten variants of HOMER3 proteins. HOMER1b and HOMER3 have been shown to form a tetramer via the carboxy-terminal domain³.

HOMER3 directly binds to type I metabotropic glutamate receptors, which act via phospholipase C to stimulate IP3-mediated release of Ca²⁺ from intracellular vesicles³.

HOMER proteins have also been implicated in axon guidance during brain development⁴.

HOMER3 can regulate transcription and play a very important role in the differentiation and development for some tissues such as muscle and the nervous system. Studies show that HOMER3 abnormal expression plays a role in acute myeloid leukemia (AML). Heterologous expression of HOMER3 in K562 cells inhibits proliferation, influences the cell cycle profile, affects apoptosis and also promotes cell differentiation⁵.