SPI1
Transcription factor PU.1 (SPI1)
Also known as: SPI1, PU.1, SFPI1
Biology & Mechanism
SPI1 encodes PU.1, a master transcription factor that is essential for microglial identity and is among the most highly expressed transcription factors in microglia. Variants at the SPI1 locus are associated with Alzheimer's disease risk. PU.1 activity regulates the expression of many microglial genes including TREM2, TYROBP, CD33, and CX3CR1. Lower PU.1 expression has been proposed to reduce microglial gene expression and thereby alter AD risk.
Open Questions
- —How precisely do SPI1 variants alter PU.1 expression in human microglia compared to other myeloid cells?
- —Can PU.1 activity level be targeted therapeutically without broadly disrupting microglial viability?
- —What is the transcriptional consequence of SPI1 risk variants on the full microglial gene regulatory network?
Sources
- A transcriptome-wide association study of Alzheimer's disease using prediction models of relevant tissues identifies novel candidate susceptibility genes (2019)
Last reviewed: June 1, 2026