Mechanistically, TBK1 inactivates RIPK1 by phosphorylating RIPK1 at Thr189, and loss of TBK1 boosts RIPK1 activation and aggravates late-onset ALS/frontotemporal dementia-like pathology,532,533 providing insights on intermolecular regulation between TBK1 and RIPK1 in ALS. Here, RIPK1 is linked to amyotrophic lateral sclerosis.