We previously identified a six-transmembrane epithelial antigen of the prostate (STEAP) 4 as a novel plasma membrane protein that is downregulated in obese patients and may play a significant role in the development of human obesity. This study was designed to identify the biological characteristics of the STEAP4 gene in human adipocytes. On the basis of oil red O staining and the expression profiles of specific markers, we demonstrated that overexpression of STEAP4 did not affect adipogenesis. 2-Deoxy-D-[3H]-glucose uptake tests showed that STEAP4 promoted insulin-stimulated glucose uptake in mature human adipocytes. Further data from quantitative real-time RT-PCR and Western blotting revealed that the adipokines tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), and leptin, which have been implicated in insulin sensitivity regulation, regulate the expression of STEAP4. Our results demonstrate that STEAP4 does not influence human adipocyte differentiation, but it participates in regulating the insulin sensitivity of human adipocytes.