Peptidase inhibitor 16 (PI16)

Peptidase inhibitor 16 (PI16) is a secreted protein belonging to the cysteine-rich secretory protein (CRISP) family, predominantly produced by specialized fibroblasts in various tissues including heart, fat, and the meninges/epi-perineurium surrounding nerves[3]. PI16 has a key regulatory role in tissue remodeling and inflammation, notably acting as an inhibitor of matrix metalloproteinase 2 (MMP2), a protease involved in extracellular matrix degradation[1][3]. It is upregulated in response to mechanical shear stress and is downregulated by inflammatory cytokines[1]. PI16 is implicated in controlling neuropathic pain by promoting the permeability of the blood-nerve barrier and facilitating immune cell infiltration into nerve tissues, making it a promising, tissue-selective therapeutic target for chronic pain and other fibrotic/inflammatory disorders[3]. PI16 expression marks a precursor fibroblast state involved in tissue homeostasis and remodeling[2]. No currently approved drugs target PI16 directly, but its inhibition shows protective effects in preclinical models of neuropathic pain[3].

Other names

CRISP9PSPBPPSEC0164UNQ289/PRO328CD364PI-16MSMBBPCysteine-rich secretory protein 9PSP94-binding proteinmicroseminoprotein beta-binding proteinprotease inhibitor 16MGC45378dJ90K10.5

Inhibits matrix metalloproteinase 2 (MMP2) by binding to an exposed loop above its active site, blocking enzymatic activity