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. Mutations in the LAMP2 gene are known to cause Danon disease, highlighting its importance in human health [2,4,5].

Genetic inactivation of Lamp2 in thymic stromal cells specifically impairs the development of CD4 T cells that completed positive selection, due to defects in autophagy in lamp2-deficient cortical thymic epithelial cells (cTECs) which leads to alterations in MHC II processing and reduction in CD4 TCR repertoire diversity [1]. LAMP2 deficiency in mice also accelerates the age-associated formation of basal laminar deposits in the retina, resembling histopathological changes in age-related macular degeneration (AMD), due to compromised lysosomal degradation and increased exocytosis in LAMP2-deficient retinal pigment epithelium (RPE) cells [6]. In engineered Aza-resistant MDS cell lines and some AML cell lines, LAMP2 deficiency is responsible for azacytidine (Aza) resistance and hypersensitivity to lysosome and autophagy inhibitors [3].

In conclusion, LAMP2 plays essential roles in multiple biological processes. Its functions in autophagy-related pathways are crucial for T-cell development, retinal health, and response to certain drugs in MDS/AML. The use of gene knockout (KO) mouse models in these studies has significantly contributed to understanding its role in these disease-related areas.