Loss of TMEM106B and PGRN leads to severe lysosomal abnormalities and neurodegeneration in mice.

However, an obvious and highly significant accumulation of ubiquitinated proteins and autophagy adaptor protein p62 in both soluble and insoluble fractions and phosphorylated TDP‐43 (S403/S404) in the insoluble fraction was detected in the 5‐month‐old Tmem106b − / − Grn − / − brain lysates and spinal cord lysates (Fig 12 A and B).

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