G protein-coupled receptor 173 (GPR173) (GPR173)

G protein-coupled receptor 173 (GPR173), also known as GPR5, is a member of the Super Conserved Receptor Expressed in Brain (SREB) family, characterized by its high evolutionary conservation across vertebrate species (UniProt Q9NS66; HGNC 4529). Primarily localized in the hypothalamus and pituitary gland, GPR173 serves as the primary receptor for the neuropeptide Phoenixin, playing a pivotal role in the regulation of the hypothalamic-pituitary-gonadal (HPG) axis (Stein et al., 2016). Activation of GPR173 by Phoenixin stimulates the release of gonadotropin-releasing hormone (GnRH), thereby influencing the estrous cycle and reproductive functions (Treen et al., 2016). Beyond its endocrine roles, GPR173 is involved in modulating cell migration and has been implicated in the pathophysiology of certain cancers and neurodegenerative conditions (Lyu et al., 2018). The receptor typically signals through the Gs-protein/cAMP pathway, although its full signaling repertoire is still being elucidated. As an orphan receptor for many years, GPR173 represents an emerging therapeutic target for treating reproductive disorders, hormonal imbalances, and potentially metastatic cancers. Despite its biological significance, there are currently no approved small-molecule drugs or clinical-stage therapies that specifically target GPR173.

Other names

GPR5SREB3Super conserved receptor expressed in brain 3

GPR173 acts as a G protein-coupled receptor that, upon activation by ligands such as Phoenixin, typically stimulates the Gs-alpha/cAMP/PKA signaling pathway to modulate GnRH expression and secretion (Stein et al., 2016; Treen et al., 2016).