SIRPA

Signal regulatory protein alpha (CD172a)

Also known as: SIRPA, SIRPα, CD172a, SHPS-1, BIT

Biology & Mechanism

SIRPA encodes SIRPα (CD172a), an inhibitory receptor that interacts with CD47 on healthy cells to generate a 'don't eat me' signal, preventing microglial phagocytosis of live neurons. The SIRPα-CD47 axis calibrates microglial phagocytic activity and protects viable neurons. Disruption of this checkpoint may contribute to excessive synaptic or neuronal elimination in neurodegeneration. Targeting this axis is also being explored in oncology.

Open Questions

  • How does CD47 expression on neurons change with aging and neurodegeneration?
  • Can modulation of the SIRPα-CD47 axis selectively shift microglial phagocytosis toward pathological substrates (amyloid, tau) rather than neurons?
  • What is the relationship between SIRPα signaling and TREM2-driven phagocytosis?

Sources

Evidence Status

human tissuesingle-cell RNA-seqanimal modelin vitro assay

Disease Links

  • Alzheimer's disease
  • Brain aging

Last reviewed: June 1, 2026