GNA15 encodes G protein subunit alpha 15, a member of the Gq class G protein family that functions as a molecular switch in G protein-coupled receptor (GPCR) signaling 1. The protein transduces signals from GPCRs to downstream effectors, with hematopoietic-restricted expression 1. GNA15 collaborates with adapter protein TTC1 to promote HRAS activation and ERK1/2 phosphorylation independently of phospholipase C-beta signaling, and initiates EMR2-mediated signaling driving macrophage differentiation and inflammatory responses via Akt, MAPK, and NF-kappa-B activation (UniProt annotation). GNA15 is tandemly duplicated with GNA11 on chromosome 19 in mice and chromosome 19 in humans 2. Clinically, GNA15 demonstrates oncogenic potential across multiple malignancies. In pancreatic ductal adenocarcinoma, ectopic GNA15 expression correlates with poor prognosis, driven by 5' promoter demethylation; knockdown reduces cell motility and invasiveness 3. In ovarian cancer, GNA15 serves as a hub gene positively correlated with M2-like tumor-associated macrophage infiltration, predicting unfavorable outcomes 4. GNA15 overexpression promotes drug resistance in B-cell acute lymphoblastic leukemia via AMPK-mediated fatty acid oxidation activation 5. In triple-negative breast cancer, GNA15 overexpression associates with aggressive tumor clusters and poor survival; knockdown attenuates proliferation, migration, and invasion 6. GNA15 is downregulated in esophageal adenocarcinoma and represents a potential diagnostic biomarker 7.