Tyrosine-protein phosphatase non-receptor type 6

PTPN6 (also known as SHP-1) is a tyrosine phosphatase that negatively regulates immune signaling and receptor tyrosine kinase pathways. It dephosphorylates receptor tyrosine kinases including EGFR, PDGFR, and FGFR, and when recruited to immunoreceptor inhibitory motif-containing receptors, suppresses downstream signaling. The enzyme also targets cytoplasmic signaling molecules such as STING1, LCK, and STAT1, and acts as a nuclear regulator of transcription factors including NFAT5 (UniProt: P29350).

PTPN6 functions broadly in immune regulation, hematopoiesis, and inflammatory control through modulation of T-cell activation and cytokine receptor signaling. It plays roles in both cytoplasmic and nuclear processes affecting cellular differentiation and metabolic regulation.

PTPN6 is upregulated in Alzheimer's disease brain tissue. Quantitative proteomics of post-mortem AD brain versus age-matched controls revealed increased PTPN6 abundance, with a mean log2 fold-change of 0.39 (Chaparral AD proteomics). This elevation may reflect altered immune signaling or neuroinflammatory responses in the AD brain microenvironment.