Transmembrane serine protease 6 mRNA (TMPRSS6 mRNA)

Transmembrane serine protease 6 (TMPRSS6) mRNA encodes Matriptase-2, a critical liver-expressed enzyme that acts as a negative regulator of hepcidin, the master hormone of systemic iron homeostasis. Matriptase-2 functions by cleaving membrane-bound hemojuvelin (HJV), thereby inhibiting the BMP/SMAD signaling pathway that normally induces hepcidin expression. In conditions characterized by iron overload or ineffective erythropoiesis, such as beta-thalassemia and polycythemia vera, targeting TMPRSS6 mRNA with RNA-based therapeutics (siRNAs or ASOs) allows for the reduction of Matriptase-2 protein levels. This reduction leads to increased hepcidin production, which subsequently limits iron absorption from the diet and sequesters iron within macrophages, effectively lowering plasma iron levels and improving disease outcomes. Clinical development of drugs targeting this mRNA has shown promise in managing iron-related disorders by leveraging the body's natural regulatory mechanisms.

Other names

Matriptase-2 mRNATMPRSS6 messenger RNAType II transmembrane serine protease 6 mRNA

RNA interference (siRNA) or antisense oligonucleotide (ASO) mediated degradation of TMPRSS6 mRNA to reduce Matriptase-2 protein levels, thereby increasing endogenous hepcidin expression and reducing systemic iron levels.