Doppel: more rival than double to prion.

Conversion of normal cellular prion protein to the diseased form plays an essential role in transmissible spongiform encephalopathies such as mad cow disease and Creutzfeldt-Jakob disease. However, the normal physiological function of prion protein remains elusive. Doppel, a German synonym of double, was initially identified as a prion-like protein due to its structural and biochemical similarities. However, emerging evidence suggests that function of prion protein is more antagonistic to Doppel than synergistic. In this review, basic biochemical and structural similarities of prion protein and Doppel are introduced; evidence demonstrating antagonistic interaction of prion protein with Doppel is presented; and a potential novel activity of Doppel and prion protein in spermatogenesis, which could stimulate new avenues for research, is discussed.