MCOLN3 is a calcium-permeable cation channel localized to endolysosomal membranes that regulates critical cellular trafficking and degradation pathways 1. As a nonselective cation channel with inwardly rectifying activity, MCOLN3 mediates calcium release from endosomes and lysosomes to the cytoplasm, contributing to endosomal acidification and membrane fusion events 2. MCOLN3 plays a central role in autophagy regulation, functioning as a downstream effector of phosphatidylinositol-3-phosphate (PtdIns3P) to provide calcium for autophagosome biogenesis and maturation 34. The channel forms heteromers with MCOLN1 to supply calcium for autophagosome-lysosome fusion, with this process decoding through the calcium sensor synaptotagmin 5 4. During autophagy induction, MCOLN3 activation at phagophores inhibits MTORC1 activity through positive feedback, promoting autophagic flux under nutrient deprivation 2. Pathologically, MCOLN3 dysfunction impairs lysosomal acidification, allowing intracellular pathogens like Helicobacter pylori to survive 5. Conversely, aberrant MCOLN3 activation induces autophagy blockage and apoptosis in lung cancer cells 6. Mutations in MCOLN3 associate with nonsyndromic hearing loss and Griscelli syndrome, reflecting its specialized roles in hair cell mechanotransduction and melanosome trafficking 1.