TBK1 Mutations in ALS and Frontotemporal Dementia Linked to Problems in Cell Cleanup and Protein Balance

Mutations in the TBK1 gene are a significant genetic link between Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD).

• TBK1 is a multifunctional kinase that plays a crucial role in the autophagy-lysosome pathway.
• It regulates key processes including cargo recognition, autophagosome formation, vesicle maturation, and lysosomal fusion.
• ALS/FTD-associated mutations can lead to haploinsufficiency or disrupt the function of TBK1 through domain-specific changes.
• These disruptions may impact the autophagic functions that TBK1 coordinates, contributing to disease pathology.

Simplified