Last reviewed: June 1, 2026

2021Brain, Behavior and Immunity

INPP5D is an Alzheimer's disease risk gene implicated in microglial phagocytosis

Butler CA, et al.

Abstract summary

Characterized INPP5D (SHIP1) expression and function in human and mouse microglia. INPP5D is a phosphoinositide phosphatase that negatively regulates TREM2 signaling and phagocytosis. AD-associated INPP5D variants are associated with increased expression, suggesting that INPP5D limits microglial protective function. INPP5D inhibition enhances microglial amyloid clearance.

Evidence labels

human geneticshuman tissueanimal model

Targets

Diseases

  • Alzheimer's disease

Species

human, mouse

Methods

RNA-seq, flow cytometry, pharmacology

Therapeutic relevance

INPP5D inhibition is a potential strategy to enhance TREM2-dependent microglial function in Alzheimer's disease.

Last reviewed: June 1, 2026