Splicing factor, proline- and glutamine-rich

SFPQ (splicing factor, proline- and glutamine-rich) is a 707-amino-acid DNA- and RNA-binding protein that functions as an essential pre-mRNA splicing factor required for early spliceosome formation and the catalytic step of splicing (UniProt: P23246). It operates primarily as a heteromer with NONO and participates in multiple nuclear processes including transcriptional regulation, DNA repair, and circadian clock control. The protein binds intronic polypyrimidine tracts and interacts with spliceosomal snRNAs, and is required for assembly of nuclear speckles.

In addition to splicing, SFPQ acts as a transcriptional regulator, functioning both as an activator and repressor depending on cellular context and binding partners. It mediates transcriptional repression through interaction with SIN3A and histone deacetylases, and participates in innate immune responses via the cGAS-STING pathway. SFPQ has no documented inherited disease associations in UniProt, though it serves critical housekeeping functions across multiple cellular pathways.

In Alzheimer's disease, SFPQ is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 1.17 (Chaparral AD proteomics). This elevation was detected via TMT-labeled mass spectrometry across multiple subcellular fractions, suggesting potential involvement in AD pathophysiology, though the specific functional consequences of increased SFPQ in disease remain to be determined.