Inpp5D Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
The INPP5D gene encodes SHIP1 (SH2-containing inositol phosphatase 1), a lipid phosphatase that negatively regulates PI3K/Akt signaling and is critically implicated in microglial function in Alzheimer's disease and other neurodegenerative conditions. [1]
| Property | Value | [2]
|----------|-------| [3]
| Gene Symbol | INPP5D | [4]
| Full Name | Inositol Polyphosphate-5-Phosphatase D |
| Chromosomal Location | 2q37.1 |
| NCBI Gene ID | 3635 |
| OMIM | 601582 |
| Ensembl ID | ENSG00000168918 |
| UniProt | Q13596 |
The INPP5D gene spans approximately 47 kb and contains 13 exons. It encodes a 1190 amino acid protein with multiple functional domains:
INPP5D encodes SHIP1 (Src homology 2 domain-containing inositol phosphatase 1), a phosphatase that converts PIP3 to PI(3,4)P2, thereby negatively regulating PI3K/Akt signaling. SHIP1 modulates:
SHIP1 is primarily expressed in hematopoietic cells, including microglia in the brain.
SHIP1 hydrolyzes phosphatidylinositol (3,4,5)-trisphosphate (PIP3), the product of PI3K activation:
GWAS identified INPP5D (SHIP1) as a significant risk gene for late-onset Alzheimer's disease. Key findings:
INPP5D is expressed in:
Brain expression is restricted to microglia and infiltrating macrophages. Expression increases in response to inflammatory stimuli.
| Approach | Status | Notes |
|---|---|---|
| SHIP1 Inhibitors | Preclinical | May enhance immune response in cancer |
| SHIP1 Modulators | Research | Tune microglial activity in neurodegeneration |
| PI3K Inhibitors | Various | Downstream targeting approach |
In Alzheimer's disease, modulating SHIP1 activity may:
The study of Inpp5D Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Last updated: 2026-03-04
Rohrschneider LR, Fuller JF, Wolf I, et al. Structure, function, and biology of SHIP1. Oncogene. 2000. ↩︎
Liu Q, Sasaki T, Kozieradzki I, et al. SHIP1 is a negative regulator of dendritic cell development. Immunity. 2009. ↩︎
Kerr WG. SHIP and inflammation. Nat Rev Immunol. 2004. ↩︎
Takai T, Tsui M, Miyazaki K, et al. SHIP1 in immune cell signaling and disease. J Clin Immunol. 2014. ↩︎