MCOLN1 (mucolipin TRP cation channel 1) is a lysosomal calcium and cation channel that plays a central role in autophagy regulation and lysosomal homeostasis. As a nonselective cationic channel localized to late endosomes and lysosomes 1, MCOLN1 mediates the release of divalent cations including Ca2+, Zn2+, and Fe2+ from lysosomes to the cytosol 21. MCOLN1 regulates multiple cellular processes by controlling lysosomal ionic balance, including endocytosis, exocytosis, lysosomal biogenesis, and autophagy completion 1. Mechanistically, MCOLN1 activity is regulated by the AMPK-PIKFYVE-PtdIns(3,5)P2 pathway 3, and zinc influx through MCOLN1 blocks autophagosome-lysosome fusion by disrupting STX17-VAMP8 SNARE interactions 2. Additionally, MCOLN1-mediated lysosomal exocytosis triggered by AKT phosphorylation promotes ferroptosis defense 4, and MCOLN1 participates in mitochondrial quality control through ROS-activated calcium release 5. Clinically, MCOLN1 mutations cause Lisch epithelial corneal dystrophy (autosomal dominant) 6 and mucolipidosis IV 7. MCOLN1 represents a therapeutic target: agonists (ML-SA5, MK6-83) suppress oncogenic autophagy in multiple cancer types 2, while selective inhibition may enhance ferroptosis sensitivity in AKT-hyperactivated cancers 4.