Cellular prion (PrPc) is a plasma membrane glycosyphosphatidylinositol-anchored protein present in neurons but also in other cell types. Protein conservation among species suggests that PrPc may have important physiological roles. Cellular and molecular approaches have established several novel features of the regulation of PrPc expression, cellular trafficking as well as its participation in copper uptake, protection against oxidative stress, cell adhesion, differentiation, signaling and cell survival. It is therefore likely that PrPc plays pleiotropic roles in neuronal and non-neuronal cells, and as such the loss of function of PrPc may be an important component of various diseases.