RGS13 is a regulator of G protein signaling that inhibits signal transduction by increasing GTPase activity of Gα(i), Gα(o), and Gα(q) subunits, driving them into inactive GDP-bound states 1. In immune cells, RGS13 primarily functions to dampen G protein-coupled receptor (GPCR) signaling in B lymphocytes and mast cells. RGS13 is highly expressed in germinal center B cells and thymic epithelial cells, where it regulates responsiveness to chemokines CXCL12 and CXCL13 by modulating heterotrimeric G-protein signaling 2. In B cells, RGS1 and RGS13 cooperatively enhance desensitization to chemokine receptor stimulation, with knockdown of both proteins augmenting chemokine-evoked calcium mobilization and cell migration 3. In mast cells, RGS13 restricts GPCR-mediated degranulation and calcium mobilization induced by ligands including sphingosine-1-phosphate and CXCL12 4. RGS13 expression is transcriptionally suppressed by p53, allowing immune responses to be modulated through p53-dependent pathways 5. Beyond cytoplasmic signaling, RGS13 translocates to the nucleus where it acts as a CREB repressor, inhibiting cAMP-dependent gene expression in lymphocytes 6. RGS13 protein stability is regulated by PKA-mediated phosphorylation, which protects it from proteasomal degradation 7. RGS13 upregulation has anti-inflammatory significance in allergic asthma models 8.