**2. Introduction to the glutaredoxin (Grx) system**

To combat oxidative stress, the body is equipped with several antioxidant enzymes in order to restore the redox balance and protect the cell. Several antioxidant enzymes such as catalase, superoxide dismutase (SOD), and thioredoxin (Trx) have been thoroughly researched due to their effectiveness and ability to directly target and scavenge ROS [2, 6–8]. However, as it is becoming more clear that PSSG is an important post-translational modification linked to oxidative stress, recent research has highlighted the glutaredoxin (Grx) system, an antioxidant system capable of reversing PSSG formation. As shown in **Figure 1**, the Grx system

**Figure 1.** Glutaredoxin and thioredoxin system.

has two main subsets in humans: the cytosolic glutaredoxin 1 (Grx1) and the mitochondrial glutaredoxin 2 (Grx2) [7]. Grx1 has garnered much interest due to its similarity with Trx1 in promoting cytosolic protection, yet Grx2 with its primary mitochondrial localization may hold a crucial role in preventing cell death. This is especially important considering that mitochondria are the primary sites of ATP and ROS production and are critically involved in balancing pro- and anti-apoptotic signals [1, 4]. However, to date, only a few studies have been published to highlight Grx2's potential roles in humans. This chapter hopes to emphasize Grx2 as an imperative and crucial antioxidant enzyme, encourage more research studying Grx2's possible roles and protein targets, and provide support for Grx2 activating drugs to treat oxidative stress-induced diseases.
