GPR174 is an X-linked G protein-coupled receptor for lysophosphatidylserine (LysoPS), a lipid mediator with pleiotropic immune and inflammatory functions 1. Structurally, GPR174 recognizes LysoPS through polar interactions with its negatively charged head group and a positively charged binding cavity accommodating the L-serine moiety, with ligand entry via a lateral opening between transmembrane domains 4-5 12. GPR174 primarily signals through Gs-coupled cAMP-PKA pathway activation, suppressing IL-2 production and regulatory T cell (Treg) activity during inflammation 1. In ischemic vascular disease, GPR174 deletion in Tregs enhances angiogenesis by upregulating amphiregulin (AREG) expression via EGR1 inhibition, improving blood flow recovery 3. Conversely, GPR174 promotes metastatic progression in esophageal squamous cell carcinoma through LysoPS-induced cAMP-PKA-CREB signaling, correlating with poor survival 4. Genetically, GPR174 polymorphisms associate with autoimmune thyroid disease susceptibility in children, with protective C alleles 56, and altered GPR174 expression correlates with vasovagal syncope pathophysiology 7. These findings establish GPR174 as a bidirectional immune regulator with therapeutic potential in vascular and autoimmune diseases, but oncogenic properties in certain malignancies.