GRM4, also known as metabotropic glutamate receptor 4, is a receptor that plays significant roles in the central nervous system. It is involved in glutamate-mediated signaling pathways, and glutamate is a key neurotransmitter in the nervous system, thus GRM4 is crucial for normal neural function [2,3].

In osteosarcoma, overexpression of GRM4 inhibits cell proliferation, migration, and invasion by interacting with CBX4 to restrict CBX4's nuclear localization and affect HIF-1α transcriptional activity [1]. Grm4-/-gene-targeted mice show accelerated radiation-induced tumor development, and GRM4 in myeloid cells selectively regulates IL23 and IL12 expression, with osteosarcoma-conditioned media affecting myeloid cell Il23 expression in a GRM4-dependent way [5].

In glioma, low expression of GRM4 is associated with poor prognosis, and its overexpression prevents the migration of human glioblastoma multiforme (GBM) cell lines in vitro, also having an impact on immune cell infiltration [4].

In breast cancer, GRM4 acts as a tumor suppressor, with its overexpression inhibiting cell proliferation, migration, and invasion, and it is regulated by miR-328-3p and miR-370-3p [6].

In conclusion, GRM4 has important functions in regulating cell behavior such as proliferation, migration, and invasion in multiple cancer types including osteosarcoma, glioma, and breast cancer. The study of GRM4 knockout mouse models has provided insights into its role in osteosarcoma development, highlighting its potential as a therapeutic target in these disease areas.