TARDBP and amyotrophic lateral sclerosis: Similar mechanisms have been reported in amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), where pathogenic variants in proteins such as FUS and TDP-43 lead to nuclear clearance, contributing to cellular toxicity in various animal models, including Drosophila. 23,43 To test whether KDM2A variants induce toxicity in an in vivo system, we generated Drosophila models expressing three missense variants (p.Tyr141Cys, p.Pro235Leu, and p.His811Asn).