TARDBP and proteostasis deficiencies: This is in line with TMEM106B being identified as a modifier in those with TDP-43 pathology5,6 but not in most other clinical FTD cohorts of non-TDP43 or unknown pathology,5 with a few exceptions7,15 potentially due to a substantial proportion of cases with FTLD-TDP pathology.7,15 Beyond FTLD-TDP, TMEM106B is associated with hippocampal sclerosis of aging,18 with or without accompanying Alzheimer type pathology, with hippocampal sclerosis in Lewy body disease,44 and with limbic-predominant age-related TDP-43 proteinopathy (LATE-NC),45 all characterized by the presence of TDP-43 proteinopathy.