The activity of cathepsin S is tightly regulated by its endogenous inhibitor, cystatin C, which also has a role in antigen presentation.

Major histocompatibility complex class II molecules interact with small peptide fragments for presentation on the surface of antigen-presenting immune cells.

Cathepsin S participates in the degradation of the invariant or Ii chain that prevents loading the antigen into the complex.

The list of proposed cathepsin S substrates includes laminin, fibronectin elastin, osteocalcin and some collagens.

The expression of cathepsin S can be triggered by proinflammatory factors secreted by tumor cells.

Whether it has a definitive role in causing the pathology of psoriasis is as yet unknown, however in the same study it was shown to specially cleave and activate the psoriasis-associated proinflammatory cytokine IL-36γ[9] Cathepsin S has a role in nociception, including itch and gastrointestinal pain.

The mechanism by which cathepsin S leads to itch and pain is consistent with the capacity of this cysteine protease to activate protease-activated receptors 2 and 4.

[10][6] Synthetic inhibitors of cathepsin S participated in numerous preclinical studies for the immune disorders including rheumatoid arthritis.

[12] This is because the cysteine enzyme can no longer act together with other proteases to break up the brain extracellular matrix.

Scientists have just announced that this enzyme predicts death, as it has been shown to be associated with both heart disease and cancer.