RGS18 is a GTPase-activating protein that negatively regulates G protein-coupled receptor signaling by increasing GTPase activity of Gαi and Gαq subunits, driving them to their inactive GDP-bound state 1. Beyond its canonical G protein regulatory function, RGS18 exhibits context-dependent roles in hematopoiesis and immune regulation. In platelets, RGS18 and RGS10 have complementary functions in limiting platelet activation and promoting platelet production and survival 1. RGS18 is reciprocally regulated by the transcription factor Gfi1b and differentially controls erythroid versus megakaryocytic lineage specification through modulation of MAPK signaling and transcription factors Fli1 and Klf1 2. Clinically, RGS18 has emerged as a multifaceted disease regulator: platelet-derived RGS18 protects circulating tumor cells from NK cell surveillance by promoting HLA-E expression through AKT-GSK3β-CREB signaling, facilitating pancreatic cancer metastasis 3. Genetic studies identify RGS18 variants associated with platelet aggregation and thrombosis risk 4, and circulating RGS18 mRNA levels are significantly downregulated in gastric cancer patients, suggesting utility as a diagnostic biomarker 5. RGS18 polymorphisms have been associated with silent brain infarction risk in Asian populations 6, and proteomic analysis links RGS18 to preeclampsia pathogenesis through blood pressure regulation pathways 7.