G protein-coupled receptor 109A

G protein-coupled receptor 109A (GPR109A), also known as HM74A, is a member of the GPCR superfamily. It is primarily recognized for its role in mediating anti-inflammatory effects and maintaining intestinal barrier integrity, especially upon activation by specific endogenous ligands such as butyric acid and β-hydroxybutyric acid. Activation of GPR109A regulates tight junction proteins, reduces inflammation via inhibition of NF-κB signaling pathways, and supports mucosal immunity by promoting IgA secretion. GPR109A has been implicated as a therapeutic target due to its broad regulatory roles in diseases including dyslipidemia, intestinal disorders, sepsis, neuroinflammation and metabolic diseases.

Other names

HM74A

Agonism of GPR109A leads to downstream signaling cascades via G-protein activation, resulting in anti-inflammatory effects and regulation of intestinal barrier function.