GRN and neuronal ceroid lipofuscinosis: Lipofuscin accumulation may occur with partial loss of progranulin expression [16, 24, 25], but the dramatic increase in accumulation in Grn-null mice and the dramatically different clinical presentation of GRN-null patients with NCL compared to heterozygous GRN-null patients with FTLD do not support a direct dose dependence of these phenotypes on progranulin expression levels.