RGS16 is a regulator of G protein-coupled receptor (GPCR) signaling that functions as a GTPase-activating protein, increasing the GTPase activity of G protein alpha subunits to drive them into their inactive GDP-bound state 12. Beyond canonical GPCR regulation, RGS16 has emerged as a multifunctional protein with significant disease relevance. In pancreatic β cells, RGS16 promotes insulin secretion and β-cell proliferation by limiting inhibitory somatostatin signaling 3. Conversely, RGS16 suppresses CD8+ T cell survival in tumors by disrupting Erk1 activation through interaction with scaffold protein IQGAP1, promoting T cell exhaustion and limiting immunotherapy efficacy 4. In cancer contexts, RGS16 is elevated in colorectal and gastric cancers, where it restrains apoptosis and ferroptosis through MAPK signaling disruption, correlating with poor prognosis 56. Clinically, RGS16 represents a dual-edged therapeutic target: its upregulation in tumors-restricted promoters enhances CAR-T cell efficacy 7, while RGS16 inhibition in tumor-infiltrating lymphocytes synergizes with PD-1 blockade to enhance antitumor responses. In schizophrenia, RGS16 upregulation suggests enhanced GPCR signal inactivation 8. These findings position RGS16 as a biomarker and potential therapeutic target across cancer, immunotherapy, and neuropsychiatric disorders 9.