OPTN and amyotrophic lateral sclerosis: Notably, pTDP-43 pathology was relatively sparse across all layers in the single heterozygous TARDBP (M337V) mutation case analysed, but was widespread and severe in homozygous ALS-OPTN (R217X), particularly within layer II and V and at the grey/white matter border (Fig. 2a,d; Supp Figure 2).