Why Lysosomal Ion Channels Matter

With aging, the autophagy-lysosomal pathway (ALP) progressively declines, leading to impaired protein turnover, organelle damage, and the accumulation of toxic aggregates — including alpha-synuclein, Aβ, p-tau tangles, TDP-43, and lipofuscin — seen across major neurodegenerative diseases. Lysosomal ion channels such as TRPML1, TMEM175, ATP12A2, and TPC2 function as key signaling sensors that regulate calcium homeostasis, membrane potential, and proton gradients required for ALP activation. By directly modulating these channels — the control nodes capable of reactivating and rejuvenating the aging ALP — we address the upstream biology driving neurodegeneration rather than chasing downstream consequences.