RGS4 (Regulator of G Protein Signaling 4) is a critical negative regulator of G protein-coupled receptor (GPCR) signaling. RGS4 functions as a GTPase-activating protein that accelerates GTP hydrolysis of Gα subunits, driving them into their inactive GDP-bound state and terminating GPCR-mediated signals 1. This activity can be modulated by post-translational modifications: phosphorylation and palmitoylation of Gα proteins inhibit RGS4's GTPase activation function. RGS4 displays tissue-specific and GPCR-selective interactions, with cardiac RGS4 expression being selectively upregulated in human heart failure 12. RGS4 is implicated in cardiac pathophysiology, with evidence suggesting protective effects against atrial fibrillation in knockout studies 1. Beyond cardiology, RGS4 is considered a candidate risk gene for schizophrenia, with several genetic polymorphisms (rs2661319, rs10759) showing associations with schizophrenia risk, particularly in East Asian populations 34. Additionally, RGS4 has been identified as a prognostic biomarker in glioblastoma when incorporated into multi-gene risk models 5. RGS4 protein stability can be regulated through N-terminal cysteine modifications via the hypoxia-dependent ADO enzyme 6. Small organic molecule inhibitors targeting RGS4 are under development for therapeutic applications 2.