TBK1 Loss Drives Motor Neuron Death Through Impaired Mitophagy and Metabolic Collapse

h-var-b7e8e12838

This hypothesis proposes that loss-of-function mutations in TBK1 contribute to ALS pathogenesis primarily through disrupted mitochondrial quality control in motor neurons, leading to bioenergetic failure and selective neuronal death. TBK1 normally phosphorylates autophagy receptors OPTN and p62, which are essential for targeting damaged mitochondria for mitophagy. When TBK1 function is lost, defec