This interaction disrupts cellular connectivity, tissue structural integrity, and homeostasis, contributing to disease pathogenesis.In ALS, PDK1 dysregulation not only impairs energy metabolism by suppressing the TCA cycle and glycolysis—leading to reduced oxidative phosphorylation and ATP production—but also plays a significant role in the WNT/β-catenin pathway. This evidence concerns the gene PDK1 and amyotrophic lateral sclerosis.