SIRPα acts as inhibitory receptor and interacts with a broadly expressed transmembrane protein CD47 also called the "don't eat me" signal.

[5] This is analogous to the self signals provided by MHC class I molecules to NK cells via Ig-like or Ly49 receptors.

SIRP β and γ have the similar extracellular structure but different cytoplasmic regions giving contrasting types of signals.

SIRP α polymorphisms are found in ligand-binding IgSF V-set domain but it does not affect ligand binding.

[9][10] Cancer cells highly expressed CD47 that activate SIRP α and inhibit macrophage-mediated destruction.