LAMP2, short for lysosomal-associated membrane protein 2, is a well-recognized mediator of autolysosome (AL) maturation. It is involved in the autophagy-lysosomal protein degradation pathway, which is crucial for various cellular processes [1,3]. Mutations in the LAMP2 gene are associated with Danon disease, a rare X-linked dominant multisystemic disorder [2,3,4].

In thymic stromal cells, genetic inactivation of Lamp2 specifically impairs the development of CD4 T cells that completed positive selection. This is due to defects in autophagy in Lamp2-deficient cortical thymic epithelial cells (cTECs), which are linked to alterations in MHC II processing and a reduction in CD4 TCR repertoire diversity [1]. In LAMP2-deficient mouse models, there are manifestations similar to Danon patients, such as the accumulation of autophagic vacuoles in heart and skeletal muscle [3]. Also, genetic LAMP2 deficiency in mice accelerates the age-associated formation of basal laminar deposits in the retina, resembling histopathological changes in age-related macular degeneration (AMD) [5].

In conclusion, LAMP2 is essential for autolysosome maturation and proper autophagy function. Gene knockout mouse models have revealed its critical roles in T-cell development, the pathogenesis of Danon disease, and the formation of basal laminar deposits in AMD. Understanding LAMP2's functions provides insights into these biological processes and disease mechanisms.