Olfactory receptor 1A1 (OR1A1)

Olfactory receptor 1A1 (OR1A1) is a G protein-coupled receptor (GPCR) belonging to the rhodopsin-like Class A family, primarily recognized for its role in detecting odorant molecules in the nasal epithelium to initiate the sense of smell [1, 2, 3]. Beyond its sensory function, OR1A1 is ectopically expressed in various non-olfactory tissues, including the liver, gut, and several types of cancer cells, where it acts as a metabolic and chemical sensor [4, 8, 12]. In the liver, activation of OR1A1 by ligands such as (-)-carvone triggers a cAMP-mediated signaling cascade that reduces triglyceride accumulation by repressing PPAR-gamma, highlighting its potential as a therapeutic target for metabolic disorders like hepatic steatosis and obesity [2, 4, 32]. In the gastrointestinal tract, it has been shown to modulate the secretion of glucagon-like peptide-1 (GLP-1), further linking it to glucose homeostasis and diabetes management [4, 18, 24]. OR1A1 is also frequently overexpressed in various malignancies, such as hepatocellular carcinoma and breast cancer, where it may serve as a biomarker or influence tumor cell proliferation and differentiation [5, 14, 19, 21]. Despite its promise as a drug target, the development of OR1A1-targeted therapies is hindered by the structural complexity of olfactory receptors and the challenges associated with their heterologous expression and purification [9, 30, 31].

Other names

OR17-7OR17-11Olfactory receptor family 1 subfamily A member 1HsOR17.1.7ORL512ORL741

Activation of OR1A1 in the liver increases cAMP levels, inducing PKA activity and phosphorylation of CREB, which upregulates HES-1; HES-1 then represses PPAR-gamma expression, leading to reduced triglyceride synthesis and lipid accumulation [2, 4, 8, 32]. In enteroendocrine cells, OR1A1 activation stimulates the secretion of glucagon-like peptide-1 (GLP-1) [4, 18, 24].