Polypyrimidine tract-binding protein 1

Polypyrimidine tract-binding protein 1 (PTBP1, also known as PTB) is an RNA-binding protein that regulates pre-mRNA splicing and alternative splicing events. It binds to polypyrimidine-rich sequences within introns and can modulate exon inclusion or skipping by promoting RNA looping and facilitating U2 snRNP recruitment (UniProt: P26599). PTBP1 has established roles in tissue-specific splicing, including repression of MAPT/Tau exon 10 inclusion and regulation of PKM isoform expression through selective exon skipping.

In the context of neurological disease, PTBP1's regulatory function over Tau splicing is particularly relevant to tauopathies. The protein is upregulated in post-mortem Alzheimer's disease brain tissue compared to age-matched controls, with a mean log2 fold-change of +0.76 (Chaparral AD proteomics), detected across a single subcellular fraction in TMT-labeled quantitative mass spectrometry analysis. This elevation may alter the balance of Tau isoforms, potentially affecting disease pathology and warranting further investigation of PTBP1 as a disease-modifying factor in AD.