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338 Conversely, consistent with the notion that many LSDs result from genetic mutations that disrupt the folding of the encoded protein, it has been observed in vitro that UPR or HSR activation (leading to the upregulation of molecular chaperones) can restore some enzyme activity, e.g., for Gauchers disease-associated -glucocerebrosidase ( GBA1 ) mutations and NiemannPick disease, type C-associated NPC1 mutations