By examining altered transcriptional and proteomic profiles resulting from decreased INPP5D activity, our study suggests three potentially overlapping avenues for linking INPP5D function to microglial activation and elevated risk for AD: (1) altered inflammasome activity within microglia; (2) immune sensing pathways that would affect microglia recognition and engulfment of Aß; and (3) as-of-yet undefined signaling mechanisms that affect the expression of other proteins linked to LOAD pathogenesis through GWAS. Here, INPP5D is linked to Alzheimer disease.