The G-protein-coupled receptor 34 (GPR34) is currently classified as an orphan receptor of the P2Y₁₂-like receptor group. The receptor belongs to the super family of G-protein coupled receptors (GPCRs)¹.

The N-terminus of human GPR34 has three putative N-glycosylation sites (NXS/T), and the C-terminus has a cysteine residue which is palmitoylated in many GPCRs. GPR34 contains several putative phosphorylation sites primed by a serine or threonine in the C-terminus².

GPR34 is highly expressed in immune cells such as mast cells, macrophages, microglia, and immune system–derived cell lines (HL-60, K562, WEHI-3B, RAW 264.7, P815). Studies shows that GPR34 function is required to arrest microglia in the M0 homeostatic non-phagocytic phenotype and downregulation of GPR34 promotes the neurodegenerative microglia phenotype^2,3,4.

GPR34 is linked to several human diseases including immunological diseases and cancer. Most known effects of GPR34 are immune function-related. For example, GPR34 is significantly down-regulated in Mycobacterium tuberculosis-infected macrophages; GPR34 mRNA is significantly lower in the cerebrospinal fluid from multiple sclerosis patients; GPR34 is significantly upregulated in the striatum and cortex of patients with Parkinson's disease but downregulated in substantia nigra. elevated GPR34 also plays a role in the progression of some tumors, such as human gastric adenocarcinoma, mucosa-associated lymphoid tissue (MALT) lymphoma, and colorectal cancer^1-3.