PRKN and Johanson-Blizzard syndrome: Whilst UBR1, to the best of our knowledge, has not previously been directly implicated in AD, it is an E3 ubiquitin ligase of the N-end rule pathway [20] and mutations in the gene are linked to the Johanson-Blizzard syndrome which is characterised by a variety of features including varied degrees of cognitive impairment [21].