RGS1 (regulator of G protein signaling 1) serves as a critical regulator of immune cell function and trafficking with significant implications for cancer immunotherapy and autoimmune diseases. The protein functions as a GTPase activating protein that inhibits G protein-coupled receptor signaling by accelerating GTP hydrolysis on G protein alpha subunits 1. In tumor immunology, RGS1 plays a paradoxical role: while tumor-intrinsic RGS1 expression enhances antigen presentation by activating the IFNγ-STAT1 pathway and promoting CD8+ T cell infiltration 1, high RGS1 expression in T cells themselves impairs their trafficking to tumors by inhibiting calcium influx and suppressing ERK/AKT activation 2. RGS1 is essential for regulatory T cell function, controlling the FOXP3-c-MYC transcriptional axis and modulating metabolic programs including autophagy and glycolysis 3. The protein also regulates alveolar macrophage phenotypes through calcium signaling-dependent pathways 4. Clinically, RGS1 polymorphisms are associated with celiac disease risk 5, and RGS1 expression patterns serve as biomarkers for immunotherapy response in gastric cancer 6 and neuroinflammation in Alzheimer's disease 7. These findings highlight RGS1 as a potential therapeutic target for enhancing anti-tumor immunity while managing autoimmune conditions.