GFRA3 is a glycosylphosphatidylinositol-anchored receptor for artemin (ARTN), a member of the GDNF family of neurotrophic factors 1. In normal physiology, GFRA3 mediates artemin binding to support survival and neurite outgrowth of sensory and sympathetic peripheral neurons through RET receptor co-signaling 1. However, emerging evidence reveals critical roles in cancer pathology. The ARTN-GFRA3 axis activates PI3K/AKT and ERK signaling through KRAS, inducing epithelial-mesenchymal transition, migration, and invasion in gastric cancer cells 2. High GFRA3 expression correlates with poor prognosis, including shorter survival and advanced disease stage 2. Tumor-derived artemin secreted by splenic erythroblast-like cells promotes hepatocellular carcinoma progression, with elevated serum artemin predicting unfavorable outcomes 3. ARTN signaling also confers drug resistance to multiple therapeutic agents including trastuzumab and paclitaxel 1. Additionally, GFRA3 expression increases sensitivity to cuproptosis-induced cell death in lung adenocarcinoma 4. Recent studies indicate GFRA3 expression on hiPSC-derived neurons enhances synaptic maturity when appropriate ligands are supplied 5. While GFRA3 mutations are not associated with Hirschsprung disease 6, the receptor shows minimal expression in glioblastoma 7.