Grm5, encoding metabotropic glutamate receptor 5 (mGluR5), is a G protein-coupled receptor belonging to the metabotropic glutamate receptor family. These receptors are obligate dimers with a large extracellular ligand-binding domain linked to a 7-transmembrane domain, and upon activation, they transmit ligand-binding signals to the G protein-coupling domain [1]. mGluR5 is involved in regulating integrative brain function and synaptic transmission, playing a key role in multiple biological processes [4].

Genetic disruption of Grm5 in mice (homozygous or heterozygous null mutations) leads to complex alterations in behaviors. For example, mGluR5 knockout (KO) mice show almost complete abolition of digging and marble burying behaviors, impaired social interaction, hyperactivity and reduced anxiety in the open-field test, and hypoactivity in the elevated zero-maze test, while motor learning in the accelerating rotarod is not impaired. These results support the importance of mGluR5 in motor and social behaviors affected in autism disorders [3]. Also, in melanoma development in mice, Grm1 can act as an oncogene in melanocytes independently of Grm5 expression, as crossing Grm5 null mice with a melanoma-prone mouse line (TG-3) did not significantly change tumor onset, progression, and metastasis [2].

In conclusion, Grm5 is crucial for normal motor and social behaviors, as demonstrated by gene-knockout mouse models. Its role in these processes provides insights into neurodevelopmental disorders like autism. Additionally, its lack of requirement for the oncogenic role of Grm1 in melanocytes contributes to our understanding of melanoma development.