Tyrosine-protein phosphatase non-receptor type substrate 1

SIRPA (tyrosine-protein phosphatase non-receptor type substrate 1), also known as SHPS-1, is a cell surface immunoglobulin-like receptor that acts as a docking protein for multiple intracellular signaling molecules including PTPN6 and PTPN11 (UniProt: P78324). The protein binds CD47 and thrombospondin-1 (THBS1), regulating receptor tyrosine kinase signaling, phagocytosis, dendritic cell maturation, and ROS production. SIRPA supports neuronal adhesion, neurite outgrowth, and may be involved in synaptogenesis and synaptic function.

SIRPA is widely expressed and functions in immune regulation and cell-cell interactions across multiple tissues. The UniProt record indicates no primary disease associations in the curated database (UniProt: P78324), though the protein's roles in neuronal support and immune signaling are consistent with broader neurobiological relevance.

In Alzheimer's Disease, SIRPA shows consistent downregulation in post-mortem brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.39 across two subcellular fractions in TMT-labeled mass spectrometry analysis. The direction of change is uniform across fractions, suggesting reduced SIRPA expression in AD brain, which may impact synaptic function and immune-mediated neuroinflammation pathways relevant to neurodegeneration.