Redox Biology and Insulin-like Growth Factor-Binding Protein-6: A Potential Relationship.

Insulin-like growth factor-binding protein 6 (IGFBP-6) is primarily recognized for its inhibitory effects on insulin-like growth factor 2 (IGF-2), regulating processes such as cell proliferation, differentiation, and survival. However, recent studies have revealed that IGFBP-6 also participates in a range of IGF-independent activities, notably in redox biology, immune regulation, and fibrosis. These IGF-independent actions involve interactions with redox-sensitive signaling pathways that influence mitochondrial metabolism, neutrophil function, and fibroblast activity, all of which are central to redox-dependent processes in inflammation and fibrosis. Despite these insights, the precise mechanisms by which IGFBP-6 modulates redox signaling remain largely unexplored. This review examines the growing understanding of IGFBP-6 beyond its classical role as an IGF-binding protein, with a focus on its involvement in redox homeostasis. By exploring these emerging roles, we aim to elucidate how IGFBP-6 contributes to redox homeostasis and to assess its potential as a therapeutic target in oxidative stress-related diseases, including fibrosis, cancer, and immune dysfunction.