UCP3 is a mitochondrial protein with high homology to the established uncoupling protein, UCP1. Its high degree of homology to UCP1 suggests that UCP3 may be a true uncoupling protein. Preliminary biochemical studies are consistent with UCP3 having uncoupling activity. However, detailed functional studies are required to understand the true biochemical and physiological purpose of UCP3. These efforts should be aided by identification of humans with inactivating mutations and/or the generation of gene knockout mice lacking UCP3.