Membrane-bound serine protease (PubMed:18976966, PubMed:20518742, PubMed:25156943, PubMed:25588876). 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:25156943, PubMed:18408718, PubMed:18976966). Interacts with HJV. The processed, activated two-chains form is released in the extracellular space. Cytoplasmic domain mediates HAMP suppression via proximal promoter element(s). The single-chain zymogen undergoes autoproteolytic processing (PubMed:20518742, PubMed:25156943, PubMed:18976966). This results in TMPRSS6 shedding from the cell surface and conversion into an activated two-chains form which is released extracellularly (PubMed:20518742, PubMed:25156943, PubMed:18976966). The process involves a trans-activation mechanism that requires TMPRSS6 oligomerization (PubMed:20518742, PubMed:25156943). The disease is caused by variants affecting the gene represented in this entry. Mutations leading to abrogation of TMPRSS6 activity are associated with IRIDA due to elevated levels of hepcidin, a negative regulator of plasma iron pool (PubMed:20232450). Belongs to the peptidase S1 family. A study described a function as serine protease towards extracellular matrix proteins in the liver; however, this article was later retracted.