Different lysosomal insults, one microglial fate.

Genetic associations point to a connection between lysosomal function and neurodegeneration. In this issue of Immunity, Balak et al. and Tejwani et al. show that genetically distinct lysosomal insults converge on a shared MITF/TFE-driven epigenetic program that underlies disease-associated microglial states, thereby connecting lysosomal dysfunction with transcriptional regulation in microglia.