RGS17 is a regulator of G protein-coupled receptor (GPCR) signaling that functions as a GTPase-activating protein (GAP) to negatively regulate G protein signaling 1. The protein selectively binds to Gα subunits, particularly GNAZ and GNAI2, and accelerates their GTPase activity, driving them into inactive GDP-bound states 2. RGS17 contains a conserved RGS box domain conferring GAP activity and an amino-terminal cysteine string motif enabling protein interactions and covalent modification 1. Clinically, RGS17 is aberrantly upregulated in multiple human malignancies including lung, prostate, breast, colorectal, and hepatocellular carcinomas, despite being normally restricted to the central nervous system 34. In cancer cells, RGS17 promotes tumor progression through paradoxical enhancement of cAMP-PKA-CREB signaling and increased cyclic AMP levels, driving cell proliferation, migration, and invasion 35. RGS17 knockdown significantly reduces tumor growth and metastatic potential in colorectal and lung cancer models 56. In triple-negative breast cancer, RGS17 upregulation via the NRF2 pathway correlates with poor prognosis 7. These findings position RGS17 as a promising therapeutic target; selective small-molecule RGS17 inhibitors could potentially treat multiple cancer types 84.