CTSD and ischemic stroke: Accumulating evidence suggests that disease-associated microglia are activated by sensing the neurodegeneration-associated molecular patterns in the brain, such as apoptotic neurons, myelin debris, and lipid degradation products41, and play a protective role by expressing a unique signature of genes relating to phagocytosis and lipid metabolism23, such as Apoe, Ctsd, Lpl, Tyrobp, Trem2, Cd9, and Cst7, etc. Interestingly, the Nhe1 cKO microglia showed similar upregulation of these genes after ischemic stroke.