TRPML1 is a member of the Transient Receptor Potential ion channel superfamily.
The channel is located primarily on lysosomes, which serve as the recycling centers within a cell. Cellular components (proteins, lipids, and whole organelles) are broken down to building blocks by enzymes in the lysosome and the parts are then reused. The enzymatic activity of the lysosome is regulated in part by the ionic composition of the lysosome including the pH, calcium, and sodium concentrations. Dysregulation of the lysosome occurs in many lysosomal storage and neurodegenerative diseases. We believe that modulating TRPML1 will restore activity to the lysosome and health to the affected cells.
TRPML1 normally functions to regulate and maintain the ionic composition in the lysosome, and mutations in TRPML1 lead to Mucolipidosis Type IV, which is typified by lysosomal dysfunction and toxic accumulation of proteins and lipids that have not been efficiently recycled.
1) Stimulating TRPML1 can drive clearance by enhancing activity of multiple lysosomal enzymes
2) TRPML1 activation can impart longer term cellular changes by impacting gene transcription
3) Ca2+ release through TRPML1 can stimulate membrane repair and recycling via lysosomal fusion with the plasma membrane