TARDBP and amyotrophic lateral sclerosis: Therefore, to determine whether NLK dysregulation may be involved in ALS/FTLD-TDP disease pathogenesis, we initially investigated NLK expression in progranulin knockout (GRN-KO) mature brain organoids (mbOrgs), an FTLD-TDP model that recapitulates key pathological features of disease, including TDP43 mislocalization, phosphorylated TDP43, and characteristic missplicing of TDP43 substrate RNAs (57).