RGS7 (regulator of G protein signaling 7) functions as a GTPase activator that forms complexes with GNB5 to regulate G protein-coupled receptor signaling cascades 1. The RGS7-GNB5 complex acts as a signaling inhibitor by promoting GTPase activity of G protein alpha subunits like GNAO1, driving them into their inactive GDP-bound form 1. RGS7 exhibits unique structural characteristics, including formation of complexes with the orphan GPCR GPR158, which functions as a metabotropic glycine receptor 12. This GPR158-RGS7 complex is regulated by glycine binding and modulates neuronal excitability in cortical neurons, with implications for mood and cognition 12. Beyond its canonical neuronal functions, RGS7 plays pathological roles in disease. It acts as a tumor suppressor in melanoma, where recurrent mutations (11% of cases) lead to protein destabilization and increased cancer cell migration and invasion 3. In cardiac tissue, RGS7 forms complexes with CaMKII and drives chemotherapy-induced cardiotoxicity through oxidative stress and mitochondrial dysfunction 4. RGS7 also mediates cardiokine signaling by promoting TGFβ1 release, contributing to multi-organ damage including hepatotoxicity following chemotherapy exposure 5. Additionally, RGS7 silencing appears protective against atrial fibrillation by activating cGMP-PKG signaling pathways 6.