GPR55

GPR55 is an orphan G protein-coupled receptor activated by the endogenous lipid lysophosphatidylinositol (LPI) and modulated by various cannabinoids; it has occasionally been informally nicknamed "CB3", though its low sequence homology with CB1/CB2 (~13%) and distinct Gα12/13-coupled signaling argue against formal classification as a cannabinoid receptor. Ryberg et al. (2007, British Journal of Pharmacology 152:1092) reported cannabinoid activity at GPR55, with CBD acting as an antagonist and some THC analogs as agonists; subsequent literature is mixed, and standardization of GPR55 pharmacology remains incomplete. GPR55 is expressed in the CNS, adrenal cortex, GI tract, and many cancer cell lines, and has been implicated in bone homeostasis, cancer proliferation, inflammatory pain, and insulin secretion. ⚠️ Its classification and cannabinoid pharmacology remain partially unresolved. → See also: CBD, CB1 receptor, CB2 receptor.