Is there any mammalian prion disease not linked to the PRNP gene (which is fairly conserved across mammals)?
At first I assumed that 'prions' came in many flavors, like virus. However from my brief lit search, it seems like people are talking about (p)rion proteins as if they were't all (P)rion proteins (PRNP). If all mammalian 'prion' disease can be traced to a single conserved gene, I think the risk of another 'prion-like' disease cropping up is pretty low.
But then again, who knows? Prion disease still seems shrouded mystery, which I find odd given (1) how inherently interesting this topic seems, and (2) we've gotten really, really good at molecular biology.
I feel like we are missing a key piece of the puzzle when it comes to understanding prion disease. The literature seems to want people to conceptualize the disease etiology as such: an alternately folded (disease causing) variant of PRNP protein (PrPs) bumps into a normal version of PRNP (PrPc), causing a normal copy of PrPc to also misfold into PrPs. Rinse, repeat. So you can basically think of it like an enzyme that catalyzes a conformational change on versions of itself, in a feed-forward cascade. I feel like an alternative hypothesis however, could be one of an autoimmune response. The mammalian immune system, particularly the antibody system, is mind blowing. This system can recognize virtually any foreign protein -- it can even recognize specific sub-moieties and conformations of proteins (antigens). It must, do this while never mistaking an endogenous protein to be foreign; if it does, you get an autoimmune disease. My idea is basically that PrPs is just slightly different enough from PrPc to get tagged as foreign by the antibody system (which it absolutely can do, given that we can perform western blots to detect the PrPs variant), but also just similar enough for the antibody system to mistake some endogenous PRNP for the foreign version.