GPR108 is a seven-transmembrane GOLD domain-containing protein that functions as a critical entry factor for adeno-associated virus (AAV) transduction and an immune signaling regulator. Structurally, GPR108 belongs to the GOST (GOLD domain seven-transmembrane helix) protein family 1 and exhibits LUSTR domain topology similar to G-protein coupled receptors 2. Functionally, GPR108 is essential for AAV transduction across most serotypes except AAV5, with localization primarily to the Golgi apparatus where it mediates viral escape and trafficking from endosomes to the nucleus 34. Both GPR108 N- and C-terminal domains are required for AAV transduction 4. In innate immunity, GPR108 acts paradoxically as a negative regulator of Toll-like receptor (TLR)-triggered responses by suppressing MyD88 ubiquitination and NF-κB/IRF3 signaling, though it can activate NF-κB when overexpressed 5. Clinically, GPR108 represents a promising cancer therapeutic target; its depletion inhibits cancer cell survival, and the natural compound gambogic acid selectively targets GPR108 to block NF-κB signaling and suppress tumor growth 6. The absence of GPR108 in bird genomes correlates with reduced AAV transduction efficiency in avian species, highlighting its evolutionary and functional importance 7.