RGS22 is a regulator of G protein signaling that inhibits heterotrimeric G protein signaling by increasing GTPase activity of Gα subunits, driving them into inactive GDP-bound states 1. The protein localizes to cytoplasmic and nuclear compartments, with testis-specific expression where it interacts with GNA12, GNA13, and GNA11 subunits and plays a role in spermiogenesis 1. RGS22 expression is significantly decreased in azoospermic testes 1. In cancer contexts, RGS22 functions as a tumor suppressor. It inhibits pancreatic adenocarcinoma cell migration through G12/13-mediated suppression of stress fiber formation and F-actin reorganization 2. RGS22 overexpression reduces epithelial cancer cell invasion and metastatic potential in esophageal cancer models 3. Conversely, RGS22 downregulation increases hepatocellular carcinoma cell proliferation, migration, and invasion when targeted by miR-1260b 4. Germline sequence variants in RGS22 confer reduced basal cell carcinoma risk (OR = 0.77) 5, and reduced RGS22 expression is associated with metastatic pheochromocytoma and paraganglioma phenotypes 6. These findings position RGS22 as a potential diagnostic and prognostic biomarker for epithelial cancer metastasis with therapeutic implications for cancer prevention 3.