Gstk1, also known as glutathione S-transferase kappa 1, is a key enzyme in multiple biological processes. It is involved in maintaining peroxisomal redox homeostasis, with its glutathione-dependent disulfide bond oxidoreductase activity playing a role in regulating the intra-peroxisomal redox state [1]. It is also associated with energy production, lipid metabolism, and adiponectin secretion and multimerization [3,5]. Additionally, it may impact insulin resistance and related metabolic diseases, as well as sperm quality [3,4].

In five mouse HCM models of different etiologies, Gstk1 was significantly downregulated. Gene-gene functional interaction network analysis suggested correlative expression of Gstk1 with other genes. Knocking out gstk1 in zebrafish increased the expression of certain sarcomere genes and affected cardiac function, indicating that Gstk1 downregulation might be a common mechanism underlying HCM, possibly through increasing oxidative stress [2]. In HEK-293 cells, ablation of Gstk1 did not change the basal intraperoxisomal redox state but significantly extended the recovery period of the peroxisomal glutathione redox sensor upon treatment with thiol-specific oxidants, demonstrating its role in peroxisomal glutathione regulation [1].

In conclusion, Gstk1 is crucial for maintaining peroxisomal redox balance, energy and lipid metabolism, and adiponectin-related processes. Its downregulation in HCM models suggests a potential role in the molecular pathogenesis of HCM. Studies using gene-knockout models in mice and zebrafish have provided valuable insights into its functions and implications in disease, helping to understand the underlying mechanisms and potentially guiding the development of new therapeutic strategies for related diseases.