Taken together, these observations implicate two cellular compartments with distinct roles during the initial stages of orally-acquired prion disease: (1) endosomal compartments active in transient transcytosis and/or degradation/storage of PrPSc (LAMP1-positive endosomes in FAE enterocytes, M cells, villous enterocytes, SED macrophages, and germinal centre TBMs, and caveosomes in submucosal smooth muscle cells) and (2) the cell surface of FDCs and enteric neurons, where prion replication most likely occurs. This evidence concerns the gene LAMP1 and prion disease.