The Hyaluronidase, TMEM2, Promotes ER Homeostasis and Longevity Independent of the UPR.

Cells have evolved complex mechanisms to maintain protein homeostasis, such as the UPR, which are strongly associated with several diseases and the aging process. We performed a whole-genome CRISPR-based knockout (KO) screen to identify genes important for cells to survive ER-based protein misfolding stress. We identified the cell-surface hyaluronidase (HAase), Transmembrane Protein 2 (TMEM2), as a potent modulator of ER stress resistance.