GNA11 encodes a heterotrimeric G protein alpha subunit that functions as a critical transducer of G protein-coupled receptor (GPCR) signaling 1. The protein cycles between inactive GDP-bound and active GTP-bound states, with GPCR activation promoting GDP release and GTP binding 1. GNA11 primarily signals through phospholipase C-beta activation, generating diacylglycerol and inositol 1,4,5-trisphosphate for downstream signal propagation 1. It also transduces FFAR4 signaling in response to long-chain fatty acids and mediates OXGR1-dependent respiratory epithelial signaling for mucociliary clearance. Additionally, GNA11 participates in endothelial mechanotransduction, distinguishing between protective laminar and inflammatory disturbed blood flow patterns 2. GNA11 mutations are clinically significant in multiple disorders. Somatic GNA11 mutations are implicated in Sturge-Weber syndrome, a neurovascular disorder featuring facial capillary malformations, brain vascular abnormalities, and seizure risk 3. More prominently, GNA11 mutations drive uveal melanoma, the most common primary intraocular malignancy in adults, typically co-occurring with GNAQ mutations 4. GNA11 mutations also characterize malignant blue melanomas and certain sellar melanocytomas, where genetic analysis helps differentiate primary tumors from cutaneous melanoma metastases 5. Germline GNA11 mutations cause familial hypocalciuric hypercalcemia 2 and autosomal dominant hypocalcemia 2. These disease associations underscore GNA11's role in critical cellular signaling networks affecting vascular, neural, and metabolic homeostasis.