INHBE (Inhibin beta E chain / Activin E)

Class

siRNA (RNA interference therapeutic)

Pathway

Activin/Inhibin (TGF-beta superfamily) signaling in adipose tissue — INHBE-encoded Activin E acts on ActRIIA/ActRIIB receptors to suppress adipocyte lipolysis; siRNA-mediated knockdown of hepatic INHBE increases lipolysis and reduces fat mass, positioning HRS-5817 as an anti-obesity/weight-loss agent (same target class as Alnylam's ALN-INHBE / Arrowhead's ARO-INHBE programs)

INHBE is a gene that encodes Activin E, a hormone-like signaling protein belonging to the transforming growth factor-beta (TGF-beta) superfamily. Activin E is produced mainly in the liver and acts on fat tissue, where it binds activin receptors (ActRIIA/ActRIIB) on adipocytes (fat cells) and restrains lipolysis, the breakdown of stored fat into free fatty acids for use as energy. Human genetic studies have linked reduced INHBE activity to a favorable body-fat profile, suggesting that lowering Activin E levels could increase fat breakdown and reduce fat mass. This mechanism is approached using small interfering RNA (siRNA), a class of oligonucleotide therapeutics that binds to the messenger RNA copy of a gene and marks it for degradation, preventing the corresponding protein from being made. By silencing INHBE production in the liver, this approach aims to lower circulating Activin E, releasing the brake on lipolysis and shifting the body toward using fat stores. This positions INHBE knockdown as a metabolic strategy relevant to obesity and related conditions where excess fat mass and impaired fat metabolism play a central role.