Understanding HAIs: Ally proteins in the fight against cancer

Understanding how HAI‐1 and HAI‐2 regulate the epithelial serine protease matriptase may hold the key to curing epithelial‐derived cancer. HAIs are serine protease inhibitors that inhibit matriptase and have a poorly understood effect on the presence of matriptase protein in cells. In this issue of The FEBS Journal, Yamashita et al. provide much‐needed new insights into this effect, describing it as a ‘chaperone‐like function’ of HAI‐1. However, several observations suggest that matriptase folds correctly without HAIs and that HAIs are not chaperones. We introduce the concept of ‘ally proteins’ to categorize the poorly understood function of HAIs, distinguishing them from chaperones. Comment on: https://doi.org/10.1111/febs.16348