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

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 F 420 H 2 :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.