Inhibin subunit beta E (Activin E) (INHBE)

Inhibin subunit beta E (INHBE), also known as Activin E, is a member of the transforming growth factor-beta (TGF-beta) superfamily that is almost exclusively expressed in the liver (UniProt: P58166). Unlike other activins with pleiotropic effects, Activin E functions as a hepatokine that plays a specialized role in regulating peripheral energy metabolism and body fat distribution (PubMed: 35914141). Large-scale human genetic studies have demonstrated that individuals with loss-of-function mutations in the INHBE gene exhibit a favorable metabolic profile, characterized by reduced abdominal adiposity, lower triglyceride levels, and a significantly decreased risk of developing type 2 diabetes (Regeneron Genetics Center; Nature Communications, 2022). As a therapeutic target, the Activin E signaling pathway is being explored primarily for the treatment of obesity and metabolic disorders. By inhibiting the Activin E ligand using monoclonal antibodies, researchers aim to redirect fat storage away from visceral depots and improve systemic insulin sensitivity. This approach is particularly attractive because the liver-specific expression of INHBE suggests that targeted antagonism may have fewer systemic side effects compared to broader TGF-beta or activin inhibitors. Current drug development efforts, notably by companies like Regeneron, are focused on validating these genetic insights through clinical candidates that neutralize Activin E signaling to combat the global burden of cardiometabolic disease.

Other names

Activin beta-EInhibin beta E chainActivin EINHBE

Antagonism of Activin E signaling to mimic the metabolic benefits of loss-of-function genetic variants, leading to improved fat distribution and insulin sensitivity.