as dynamic surface protein functioning in signaling pathways. Specific sites along the protein bind other proteins, biomolecules, and metals. These interfaces allow specific sets of cells to communicate based on level of expression and the surrounding microenvironment. The anchoring on a GPI raft in the lipid bilayer supports claims of an extracellular scaffolding function. Diseases caused by PrP misfolding More than 20 mutations in the PRNP gene have been identified in people with inherited prion diseases, which include the following: Creutzfeldt–Jakob disease – glutamic acid-200 is replaced by lysine while valine is present at amino acid 129 Gerstmann–Sträussler–Scheinker syndrome – usually a change in codon 102 from proline to leucine fatal familial insomnia – aspartic acid-178 is replaced by asparagine while methionine is present at amino acid 129 The conversion of PrPC to PrPSc conformation is the mechanism of transmission of fatal, neurodegenerative transmissible spongiform encephalopathies (TSE). This can arise from genetic factors, infection from external source, or spontaneously for reasons unknown. Accumulation of PrPSc corresponds with progression of neurodegeneration and is the proposed cause. Some PRNP mutations lead to a change in single amino acids (the building-blocks of proteins) in the prion protein. Others insert additional amino acids into the protein or cause an abnormally short protein to be made. These mutations cause the cell to make prion proteins with an abnormal structure. The abnormal protein PrPSc accumulates in the brain and destroys nerve cells, which leads to the mental and behavioral features of prion diseases. Several other changes in the PRNP gene (called polymorphisms) do not cause prion diseases but may affect a person's risk of developing these diseases or alter the course of the disorders. An allele that codes for a PRNP variant, G127V, provides resistance to kuru. In addition, some prion diseases can be transmitted from external sources of PrPSc. Scrapie – fatal neurodegenerative disease in sheep, not transmissible to humans Bovine spongiform encephalopathy (mad-cow disease) – fatal neurodegenerative disease in cows, which can be transmitted to humans by ingestion of brain, spinal, or digestive tract tissue of an infected cow Kuru – TSE in humans, transmitted via funerary cannibalism. Generally, affected family members were given, by tradition, parts of the central nervous system according to ritual when consuming deceased family members. Alzheimer's disease PrPC protein is one of several cellular receptors of soluble amyloid beta (Aβ) oligomers, which are canonically implicated in causing Alzheimer's disease.