LAMP2 (lysosomal associated membrane protein 2) is a major lysosomal membrane component with three functionally distinct isoforms 1. LAMP2A serves as a receptor and channel for chaperone-mediated autophagy (CMA), facilitating transport of cytosolic proteins into lysosomes 1. LAMP2B is required for autophagosome-lysosome fusion in cardiomyocytes and participates in exosome biogenesis 1, while LAMP2C mediates nucleic acid autophagy 1. Beyond autophagy, LAMP2 directly inhibits the TMEM175 lysosomal cation channel to maintain acidic pH optimal for hydrolase activity 2. LAMP2 also participates in leucine-sensing pathways by binding calnexin to regulate MTORC1 signaling 3. During ferroptosis execution, elevated LAMP2A promotes CMA-mediated GPX4 degradation 4. Clinically, LAMP2 mutations cause Danon disease, an X-linked cardiomyopathy characterized by progressive cardiac hypertrophy, skeletal myopathy, and intellectual disability, typically fatal by age 25 in males 5. Gene therapy using AAV9-delivered LAMP2B demonstrated safety and efficacy in early clinical trials, with treated patients showing cardiac LAMP2 expression, stabilized left ventricular mass, and preserved cardiac function over 24-54 months 6. LAMP2 dysregulation also associates with type 2 diabetes and various neurodegenerative conditions, establishing its importance across multiple pathophysiological processes 7.