GPR55: from orphan to metabolic regulator?

GPR55 belongs to the class A family of G-protein coupled receptor (GPCRs) and its activity is regulated by a range of synthetic and endogenous cannabinoids, and by lipid-derived ligands. Cannabinoids are known to be important in controlling appetite and metabolic balance, and it is now emerging that GPR55 may have a role to play in energy homeostasis through the regulation of food intake, fuel storage in adipocytes, gut motility and insulin secretion. This review summarises our current knowledge of expression and function of GPR55 in tissues involved in metabolic regulation, the signalling cascades through which GPR55 is reported to act to exert its effects, and it comments on the difficulties in reaching firm conclusions when using GPR55 ligands of poor specificity. Understanding the role of GPR55 in energy homeostasis may provide a novel target for therapeutic intervention in obesity and type 2 diabetes mellitus.