Raphin1

Raphin1 is a selective, small-molecule inhibitor of the **PPP1R15B** (constitutive repressor of eIF2α phosphorylation, or CReP) regulatory subunit of the **protein phosphatase 1 (PP1)** complex. By specifically binding to the PPP1R15B-PP1c interface, Raphin1 prevents the dephosphorylation of **eIF2α**, thereby prolonging the **integrated stress response (ISR)** and inhibiting global protein synthesis. This mechanism is particularly relevant in diseases characterized by proteostatic stress, such as **multiple myeloma**, where Raphin1 has been shown to induce ER stress-mediated apoptosis and suppress tumor cell growth. It was originally identified as a potential therapeutic for protein misfolding diseases due to its ability to enhance the cell's natural proteoprotective mechanisms.