Membrane-bound serine protease (PubMed:18451267). Through the cleavage of cell surface HJV, a regulator of the expression of the iron absorption-regulating hormone hepicidin/HAMP, plays a role in iron homeostasis (PubMed:18451267). Interacts with HJV. The processed, activated two-chains form is released in the extracellular space. Expressed at highest levels in adult mice liver, kidney and uterus. Also strongly expressed within the nasal cavity by olfactory epithelial cells. A weak, but detectable, signal in adult mice tissues analyzed including brain, lung, heart, kidney, spleen, muscle, intestine, thymus and pancreas. No signal in residual embryonic yolk sac, developing kidney tubules or in embryonic tissues analyzed including lung, heart, gastrointestinal tract and epithelium of the oral cavity. Expressed at higher levels from 12.5 dpc to 15.5 dpc with a peak at 13.5 dpc. Expressed in the developing liver and at lower levels in developing pharyngo-tympanic tubes. Cytoplasmic domain mediates HAMP suppression via proximal promoter element(s). The single-chain zymogen undergoes autoproteolytic processing. This results in TMPRSS6 shedding from the cell surface and conversion into an activated two-chains form which is released extracellularly. The process involves a trans-activation mechanism that requires TMPRSS6 oligomerization. Mice display the phenotype named mask, characterized by progressive loss of body (but not facial) hair, microcytic anemia and female infertility, all reversible by dietary iron supplementation. The mask phenotype results from reduced absorption of dietary iron caused by high levels of hepcidin. Belongs to the peptidase S1 family.