GPR183 is a G protein-coupled receptor expressed on lymphocytes and myeloid cells that functions as a chemotactic receptor for oxysterols, particularly 7α,25-dihydroxycholesterol (7α,25-OHC) 1. In adaptive immunity, GPR183 mediates B-cell positioning during humoral responses and collaborates with CXCR5 to guide B-cell migration along the B-cell zone-T-cell zone boundary 2. GPR183 promotes follicular helper T-cell differentiation by positioning activated T-cells at follicle-T-zone interfaces. In dendritic cells, GPR183 mediates CD4+ dendritic cell accumulation in bridging channels, required for their homeostasis and ability to induce immune responses. Signaling occurs constitutively through Gi-alpha and MAPK1/3 (ERK1/2) pathways 3. Beyond adaptive immunity, GPR183 has emerged as a critical regulator in inflammatory diseases. During viral respiratory infections, oxysterol-GPR183 signaling drives excessive monocyte/macrophage infiltration; GPR183 antagonism reduces inflammation and attenuates SARS-CoV-2 severity 4. In hypertension, endothelial GPR183 promotes senescence via disruption of circadian signaling and cAMP/PKA/CREB pathways; GPR183 inhibition alleviates cardiovascular and renal injuries 5. GPR183 is also implicated in inflammatory bowel disease pathogenesis through immune cell trafficking 6, tuberculosis-induced eosinophil recruitment 7, and sepsis pathogenesis 8. These findings establish GPR183 as a therapeutic target across immune, cardiovascular, and inflammatory conditions.