LAMP2, or lysosomal-associated membrane protein 2, is a well-recognized mediator of autolysosome maturation. It is involved in the autophagy-lysosomal protein degradation pathway, which is crucial for various cellular processes [1,4].

Genetic inactivation of Lamp2 in thymic stromal cells specifically impairs the development of CD4 T cells that completed positive selection, due to alterations in MHC II processing and a reduction in CD4 TCR repertoire diversity [1]. In mice, Lamp2 deficiency leads to phenotypes similar to Danon disease in humans, including accumulation of autophagic vacuoles in heart and skeletal muscle [4].

In a LAMP2 knockdown cell model, LAMP2 deficiency reduces viral DNA replication, attenuates tau hyperphosphorylation and Aβ secretion induced by HSV-1, and genetic variants of LAMP2 are associated with AD risk [2]. In MDS/AML, LAMP2 deficiency is responsible for azacytidine resistance and hypersensitivity to lysosome and autophagy inhibitors [3]. In the retina, deletion of the Lamp2 gene in mice results in age-dependent formation of basal laminar deposits, resembling AMD-related histopathological changes [5].

In conclusion, LAMP2 plays essential roles in autophagy-lysosomal function, T-cell development, and is associated with multiple diseases such as Danon disease, Alzheimer's disease, MDS/AML, and age-related macular degeneration. Studies using Lamp2 knockout mouse models have significantly contributed to revealing its functions in these biological processes and disease conditions.