The function of GPR35 (G protein-coupled receptor 35, ENSG00000178623) is as follows. G protein-coupled receptor that binds to several ligands including the tryptophan metabolite kynurenic acid (KYNA), lysophosphatidic acid (LPA) or 5-hydroxyindoleacetic acid (5-HIAA) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways (PubMed:16754668, PubMed:19473985, PubMed:20361937, PubMed:24347166, PubMed:35148838, PubMed:35926043). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:19473985, PubMed:35926043). GPR35 can couple with G(i)/G(o)- or G(12)/G(13) classes of G alpha proteins depending on the context, mediating the inhibition of adenylate cyclase or activation Rho small GTPases, respectively (PubMed:19473985, PubMed:35926043, PubMed:36543774). KYNA-binding promotes monocyte adhesion to vascular endothelium under flow conditions, leading to G(i)/GNAI1 activation and inhibition of adenylate cyclase (PubMed:19473985). Involved in cardioprotection during ischemia by promoting mitochondrial remodeling: following KYNA-binding and G(i)/GNAI1 activation, GPR35 is internalized to the outer mitochondrial membrane, where it inhibits mitochondrial adenylate cyclase (ADCY10), allowing ATPIF1 to repress ATP synthase activity (PubMed:35926043). Stimulates lipid metabolism, thermogenic and anti-inflammatory gene expression in adipose tissue once activated by KYNA (By similarity). Plays a role in neutrophil recruitment to sites of inflammation and bacterial clearance through the major serotonin metabolite 5-HIAA that acts as a physiological ligand (PubMed:35148838). In macrophages, activation by lysophosphatidic acid promotes GPR35-induced signaling with a distinct transcriptional profile characterized by TNF production associated with ERK and NF- kappa-B activation (By similarity). In turn, induces chemotaxis of macrophages (By similarity). {ECO:0000250|UniProtKB:Q9ES90, ECO:0000269|PubMed:16754668, ECO:0000269|PubMed:19473985, ECO:0000269|PubMed:20361937, ECO:0000269|PubMed:24347166, ECO:0000269|PubMed:35148838, ECO:0000269|PubMed:35926043, ECO:0000269|PubMed:36543774}.