The earlier age of onset and increased CSVD severity in Col4a1+/SVC mice and Gould syndrome compared to sporadic CSVD could then be due to proteotoxic stress, as supported by our previous analysis of patients with a COL4A2 mutation,9 and association of ICH severity with levels of collagen IV ER retention in mice,35 and/or even lower extracellular collagen IV levels. This evidence concerns the gene COL4A2 and COL4A1/A2-related disorder.