GPR107 is a G protein-coupled receptor with a distinctive GOLD domain-seven transmembrane helix structure 1 that functions primarily in membrane trafficking and cellular signaling. The receptor mediates clathrin-dependent endocytosis of various cargo molecules, including angiotensin II receptor type 1 (AT1R) and collagen IV (COL4) 23. GPR107 serves as the cognate receptor for neuronostatin (NST), a peptide hormone that activates PKA signaling in pancreatic α-cells to regulate glucagon secretion 4 and modulates neuronal function and energetic metabolism in Alzheimer's disease through GPR107/PKA signaling 5. In disease pathology, GPR107 deficiency promotes diabetic nephropathy development by impairing AT1R internalization, leading to sustained receptor signaling that increases collagen IV synthesis and reduces matrix metalloproteinase-2 expression in podocytes 2. Conversely, GPR107 upregulation drives breast cancer invasion and metastasis by enhancing clathrin-mediated endocytosis of COL4 and activating ERK/STAT3 signaling via β-arrestin to increase MMP2 production 3. Additionally, GPR107 expression is elevated in liver cancer where a long noncoding RNA (lncGPR107) regulates its transcription through SRCAP-mediated chr9 remodeling to promote tumor-initiating cell self-renewal 6. These findings position GPR107 as a multifunctional receptor with context-dependent roles in metabolic regulation, tissue homeostasis, and cancer progression.