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The cellular prion protein (PrPC) is a truly remarkable cell surface glycoprotein. With (i) its broad expression pattern and (ii) particularly high levels in the nervous system, (iii) its critical involvement in fatal neurodegenerative diseases affecting different mammalian species, (iv) its structurally diverging bipartite buildup, (v) its high degree of evolutionary conservation and (vi) a variety of –at least suggested– functions despite (vii) a surprising lack of major phenotypic deficits when absent (as in respective knock-out animals), PrPC has raised considerable research interest over the last four decades.