Lysosomal transport

Lysosomal transport refers to the physiological process of moving ions, metabolites, and macromolecules across the lysosomal membrane, which is essential for maintaining cellular homeostasis and metabolic recycling. This complex machinery includes the vacuolar-type H+ ATPase (V-ATPase) for acidification, diverse ion channels such as TRPML1 and TPC for signaling, and specialized Solute Carrier (SLC) transporters for the export of breakdown products like amino acids and lipids [1, 13]. Beyond its role in degradation, the lysosomal transport system acts as a key signaling hub, integrating nutrient availability through the mTORC1 pathway and regulating autophagic flux [3, 4]. Defects in individual components of the lysosomal transport system lead to various Lysosomal Storage Disorders (LSDs), such as cystinosis and Niemann-Pick disease type C, where undigested materials accumulate to toxic levels [4, 13]. Furthermore, impaired trafficking is a major pathological feature in neurodegenerative diseases like Parkinson’s and Alzheimer’s, where it contributes to the failure of protein aggregate clearance [2, 5]. Therapeutic approaches target this system through substrate reduction therapies (e.g., miglustat), pharmacological chaperones that assist in enzyme transport, and the development of lysosome-targeting chimeras (LYTACs) that hijack these pathways for the degradation of extracellular and membrane proteins [6, 9, 10].

Other names

Lysosomal traffickingEndolysosomal transportLysosomal membrane transportLysosomal transport machineryLysosomal transport system

Pharmacological modulation of the lysosomal environment and its associated membrane proteins, including the activation of specific transporters to facilitate substrate export, the use of chaperones to improve enzyme trafficking, and the modulation of luminal pH or ion channel activity to restore degradative capacity.