Exerkine GPLD1 bridges liver and brain.

A recent study by Bieri et al. shows that exercise elevates hepatic glycosylphosphatidylinositol-specific phospholipase D1 (GPLD1), which cleaves endothelial tissue-nonspecific alkaline phosphatase (TNAP) to rejuvenate cerebrovascular signaling, enhance cognition in aging, and attenuate Alzheimer's-related pathology. This liver-to-brain enzymatic axis positions hepatokines as potent mediators of exercise-induced neuroprotection, which redefines systemic metabolism as a driver of brain resilience.