Figure 2: NRF2-PIN1 interaction. NRF2 remains inactive in the cytoplasm under stress-free conditions, bound to KEAP1. Under conditions of oxidative stress, PIN1 plays an essential role in the activation of NRF2. Upon NRF2 stabilization by PIN1, it can influence cellular policy in two distinct ways, depending on its localization in the cell. Interaction with the dynein motor complex and HSP90α localizes the complex to the actin cell cortex. On the other hand, when the NRF2/PIN1 complex interacts with importin α5 and importin β1, it enters the nucleus via the nuclear pore complex, and activates many genes associated with antioxidant defenses. Impaired NRF2 transactivation due to insufficient PIN1 is a feature of autism.