PTGDR2 (prostaglandin D2 receptor 2) is a G protein-coupled receptor that serves as the primary cellular target for prostaglandin D2 (PGD2) signaling. Upon ligand binding, PTGDR2 activates Gi-protein coupled pathways, leading to pertussis toxin-sensitive decreases in cAMP levels, Ca2+ mobilization, and PI3K signaling 1. The receptor undergoes ligand-induced internalization, a process regulated by multiple kinases including PKC, PKA, and GRK family members. In cancer biology, PTGDR2 mediates tumor-suppressive effects of PGD2. PGD2/PTGDR2 signaling directly inhibits cancer cell survival, proliferation, and migration while reducing chemotherapeutic resistance 2. In gastric cancer, this pathway restricts cancer stem cell self-renewal and tumorigenesis by inhibiting STAT3 phosphorylation, with reduced PGD2/PTGDR2 expression associated with poor prognosis in gastric, breast, lung, and pancreatic cancers 34. Additionally, PTGDR2 methylation status serves as an epigenetic biomarker for predicting recurrence in HPV-associated oropharyngeal cancer 5. Beyond cancer, PGD2/PTGDR2 signaling contributes to hair growth inhibition in androgenetic alopecia 6, and participates in immune regulation and allergic/inflammatory responses. These findings establish PTGDR2 as a key therapeutic target for cancer treatment and immune-related disorders.