The SIRP family: from structural diversity and signaling mechanisms to implications in immune-related disease targeted therapeutics
Abstract
Signal regulatory proteins (SIRPs) are membrane receptors on immune cells that control immune homeostasis and inflammation. Although SIRP family members share homologous extracellular domains, they differ in intracellular motifs and function: SIRPα transduces inhibitory signals, SIRPβ associates with DAP12 to trigger activation, and SIRPγ primarily modulates adhesion and T cell responses. This review compares the structure, ligand interactions, and signaling mechanisms of SIRPα, SIRPβ, and SIRPγ, summarizes their roles in cancer, autoimmunity and neurodegeneration, and surveys therapeutic strategies that target the CD47-SIRPα axis. We highlight current clinical progress, common toxicities, and open questions that must be addressed to advance SIRP-targeted therapies.
Fields of Study & Subjects
Phagocytosis and Immune Regulation
Endoplasmic Reticulum Stress and Disease
Adenosine and Purinergic Signaling
Publication details
- Journal / source
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Volume
- 17
- Pages
- 1764114–1764114
- Publication date
- 25 February 2026
- Language
- EN