TBK1 controls cell cleaning and recycling processes in human neurons

Haploinsufficiency of TBK1 is linked to familial ALS and frontotemporal dementia.

• TBK1 loss impacts key factors involved in cellular waste disposal processes, known as autophagy.
• It affects cargo receptors and initiation factors essential for autophagy.
• The phosphorylation of the late endosomal marker RAB7A is maintained by TBK1 in stem cells and their derived neurons.
• Novel phosphorylation sites in the autophagy protein SQSTM1/p62 are identified as dependent on TBK1.
• The absence of TBK1 function leads to a distinct neurodegenerative phenotype with disrupted neurite growth and lysosomal function.

Simplified