Strikingly, TMEM106B filaments form aggregates in the brain in elderly and across neurodegenerative diseases,47 with the risk allele associated with greater fibril formation48 and enhanced TDP-43 dysfunction.49 Although fibril accumulation has been found to be a common age-related phenomenon, fibril aggregates were especially abundant in patients with GRN pathogenic variants.50 Both progranulin and TMEM106B are important players in lysosomal health.47 TMEM106B is a transmembrane glycoprotein that primarily localizes to lysosomal membranes where it is proteolytically processed. The gene discussed is TARDBP; the disease is neurodegenerative disease.