INPP5D/SHIP1 is a dual regulator of endo-lysosome function and selective phagocytosis in human microglia.

ABSTRACT: INPP5D, the gene encoding SHIP1, is genetically associated with Alzheimer's disease (AD) risk and plays a central role in regulating immune function. Here, we aimed to elucidate the mechanism by which SHIP1 mediates its role in suppressing inflammatory pathways, with a focus on human microglia. Our findings illuminate an essential role for SHIP1 in endosome maturation and lysosomal function. We show that SHIP1 localizes to both the plasma membrane and to endo-lysosomal compartments and binds to the CapZ family of proteins, which are important for endosome maturation. Reduction of SHIP1 levels via genome editing impairs endosome maturation and lysosomal function, leading to lipid droplet accumulation and leakage of lysosomal cathepsin B into the cytosol, which in turn activates the N

SUBMITTER: Terzioglu G 

PROVIDER: S-EPMC12636417 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature