Gpr83, a G protein-coupled receptor, has been implicated in multiple physiological processes. It has been considered a novel therapeutic target due to its roles in regulating feeding, reward, anxiety-related behaviors, and pain [1,2,4,5,8]. It is highly expressed in the brain, spleen, and thymus, indicating its potential in treating neurological and immune disorders [5]. The neuropeptide PEN has been suggested as its ligand, though there are conflicting reports on this [1,3,4,5,7]. Other proposed ligands include FAM237A and FAM237B [6,9].

Silencing Gpr83 expression in murine dorsal root ganglia (DRG) led to down-regulation of neuronal and behavioral nociception, alleviating pathologic pain in hind paw inflammation and chemotherapy-induced peripheral neuropathy [2]. In anxiety-related behaviors, global knockdown of Gpr83 in male mice decreased such behaviors, while local knockdown in the basolateral amygdala of female mice led to more anxiety-related behaviors [8].

In conclusion, Gpr83 plays important roles in pain modulation, anxiety-like behaviors, and potentially in feeding and reward regulation. Findings from gene-knockdown mouse models have provided insights into its functions, suggesting Gpr83 as a potential target for treating pain-related and anxiety-related disorders.