STEAP proteins: Roles in disease biology and potential for therapeutic intervention

Abstract

Iron and copper are essential metal ions, and maintaining their metabolic balance is critical for organismal health. The Six-Transmembrane Epithelial Antigen of the Prostate (STEAP) protein family, comprising STEAP1, STEAP2, STEAP3, and STEAP4, plays a vital role in cellular metal homeostasis. These proteins are located on the cell membrane and are characterized by six transmembrane domains. With the exception of STEAP1, the STEAP proteins function as metal oxidoreductases due to their F₄₂₀H₂:NADP⁺ oxidoreductase (FNO)-like domain. However, STEAP1 contributes to metal metabolism through its heme group and interaction with other STEAP proteins. Beyond metal metabolism, STEAP proteins are involved in critical cellular processes, including the regulation of the cell cycle, proliferation, differentiation, and apoptosis. Notably, STEAP proteins are recognized as potential biomarkers and therapeutic targets in human cancers, particularly prostate cancer. This review outlines the structural features and functional roles of STEAP proteins in various diseases, including cancers, insulin resistance, non-alcoholic fatty liver disease (NAFLD), and benign prostatic hyperplasia, with a focus on their potential for therapeutic intervention.