Phosphorylation changes in human neurons identify TBK1 targets in ALS and FTD-related cell cleanup networks

Loss-of-function variants in TBK1 are strongly associated with familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).

• TBK1 is critical for maintaining the levels and activity of key interacting proteins involved in cellular processes.
• Phosphorylation of several endo-lysosomal proteins is regulated by TBK1 in neurons.
• Novel phospho-sites in the protein p62/SQSTM1 were identified, indicating TBK1's role in selective autophagy.
• The study provides a comprehensive overview of the phospho-proteome in developing human neurons.
• TBK1 may play a central role in ALS/FTD-related endo-lysosomal functions that support neuronal health.

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