STEAP4

STEAP4, short for Six Transmembrane Epithelial Antigen of the Prostate 4, is a member of the STEAP family of metalloreductases. Proteins in this family are characterized by six transmembrane domains and cytosolic N- and C- termini. STEAP4 is thought to function as an NADPH-dependent metalloreductase that reduces ferric iron (Fe3+) to ferrous iron (Fe2+) and cupric copper (Cu2+) to cuprous copper (Cu1+), enabling metal ion uptake in cells. Its activity is associated with endosomal or Golgi membranes, reflecting a role in cellular metal ion homeostasis.

Expression of STEAP4 is notable in adipose tissue and macrophages. The gene is inducible by inflammatory signals such as tumor necrosis factor-alpha (TNF-α), which has led to the alternative name TIARP (TNF-α–induced adipose-related protein). This regulatory pattern ties STEAP4 to inflammatory processes and metabolic regulation in adipose tissue.

In humans and model organisms, STEAP4 has been studied for its potential involvement in metabolic and inflammatory diseases. Genetic and expression studies have explored links between STEAP4 variants or dysregulated expression and traits such as obesity and insulin resistance. Experimental work in mice suggests that STEAP4 can influence inflammatory signaling and metabolic responses under metabolic stress, though the precise mechanisms and physiological significance remain under investigation. As part of the STEAP family, STEAP4 is also considered in broader research on metal ion homeostasis and its implications for health and disease.