GPR35

GPR35, or G protein-coupled receptor 35, is a class A GPCR with aliases including TDAG8 (T-cell death-associated gene 8). It couples to Gq/11 and Gi/o proteins, inducing intracellular calcium flux and adenylate cyclase inhibition when bound to ligands like kynurenic acid or 2-arachidonoylglycerol. Downstream pathways such as PLC-PKC, MAPK/ERK, and PI3K/Akt mediate its effects on cell proliferation, migration, and inflammation.
GPR35 is linked to inflammatory bowel disease (IBD)—genetic variants correlate with ulcerative colitis susceptibility—and colorectal cancer, where overexpression promotes tumor growth. Preclinical research explores GPR35 agonists for IBD (to regulate gut inflammation) and antagonists for cancer (to suppress proliferation). While no targeted drugs are approved yet, its involvement in these conditions makes it a promising therapeutic target.