Olfactory receptor family 51 subfamily E member 2 (OR51E2) (OR51E2)

Olfactory receptor family 51 subfamily E member 2 (OR51E2), also known as the prostate-specific G protein-coupled receptor (PSGR), is a member of the rhodopsin-like Class A GPCR family [1]. While originally identified as a chemoreceptor in olfactory sensory neurons, it is significantly expressed in non-olfactory tissues such as the prostate, kidney, and vasculature [3, 11]. In the prostate, OR51E2 is frequently overexpressed in cancerous tissues, where its activation can promote neuroendocrine trans-differentiation and tumor progression [8, 19]. Beyond its role in oncology, OR51E2 serves as a physiological sensor for gut microbiota-derived short-chain fatty acids like acetate and propionate, playing a critical role in regulating renin secretion and systemic blood pressure [12, 13]. Emerging research also links its activity to intestinal inflammation, skin melanogenesis, and airway smooth muscle remodeling [5, 9, 16]. Current therapeutic interest focuses on its potential as a diagnostic biomarker and a pharmacological target for castration-resistant prostate cancer [4, 8]. Recent pharmacological developments have identified specific allosteric modulators, such as the antagonist compound C80, which offer potential for treating proliferative and cardiovascular disorders [1, 20].

Other names

Prostate-specific G protein-coupled receptorPSGROlfactory receptor 78Olfr78RA1cMOL2.3MOR18-2

OR51E2 acts as a chemosensor that, upon ligand binding (such as short-chain fatty acids or odorants), activates G-protein signaling cascades involving G-alpha-olf, Gs, or G12. This leads to the activation of adenylate cyclase, elevation of intracellular cyclic AMP (cAMP) levels, mobilization of intracellular calcium, and activation of mitogen-activated protein kinases (MAPK) such as ERK1/2, ultimately modulating gene expression and cellular behavior [3, 19, 22].