Non-canonical roles of lysosomes in neurons

Abstract

Neurons are highly polarised and compartmentalised cells with organelles that are specialised to support their spatial and functional demands. This includes lysosomes, which are single-membrane-bound organelles enveloping acidic contents enriched with hydrolytic enzymes. While classically thought to be localised at the soma where they degrade waste, lysosomes have a range of dynamic nondegradative functions throughout neurons. Here, we review lysosomal dynamics and non-canonical functions in neurons, including axonal mRNA transport, mammalian target of rapamycin (mTOR) and Ca²⁺ signalling, neuronal remodelling, and interorganellar contact sites. We synthesise work across a range of model systems and species, providing insights from neurological diseases, where previous lysosomal research has focussed on proteostatic failure. This perspective highlights the need to better define lysosomal heterogeneity, compartmentalisation and specialisation in neurons.