PRNP and Norrie disease: However, the commonly used enzymes like collagenase have already been shown that can alter the protein landscape by introducing unwanted cleavages of proteins present at the EV membrane, like the cellular prion protein (PrPC) (Brenna et al., 2020), which has an important role in the pathophysiology of several ND (Laurén et al., 2009; Prusiner, 1982; Urrea et al., 2018) and may be relevant in BDEV uptake, trafficking, and function in brain pathologies (Brenna et al., 2020; D'Arrigo et al., 2021; Falker et al., 2016; Guitart et al., 2016; Heisler et al., 2018).