Two paradigmatic examples have been provided for in vivo models on the biosynthesis of FVIII and the associated deficiency hemophilia A. Malhotra and co-workers provided the first evidence on the use of a compound acting by alleviating ER stress, which represents a key event related to protein misfolding [180]. The gene discussed is F8; the disease is hyperinsulinemic hypoglycemia, familial, 4.