Given the relevance of a balanced lysosomal Ca2+ homeostasis in the correct modulation of autophagic flux useful in cleansing the cell of defective organelles and misfolded proteins, the involvement of TRPML1 in the pathogenesis of the Guamanian form of ALS (ALS/PDC) has been recently characterized [12]. The gene discussed is MCOLN1; the disease is amyotrophic lateral sclerosis.