These mice lack PGRN and develop neuropathology similar to NCL and FTD-GRN, including neuroinflammation and microgliosis,30–32 alterations in lysosomal gene expression,33,34 and accumulation of lipofuscin.35,36 In these experiments, we compared human GRN2 (hGRN2) and hGRN4, as previous studies suggested they have opposing functional activity.37 Furthermore, hGRN2 (also known as GRN F) and hGRN4 (also known as GRN A) share 50% identity at the amino acid level, and we reasoned that this would be sufficient to reveal differences in bioactivity if present (Figures S1A and S1B). Here, AGRN is linked to neuronal ceroid lipofuscinosis.