SFPQ is a multifunctional DNA- and RNA-binding protein essential for pre-mRNA splicing and involved in diverse nuclear processes. As a core spliceosome component, SFPQ binds intronic polypyrimidine tracts and facilitates splicing catalytic steps, particularly when complexed with its paralog NONO 1. SFPQ regulates signal-induced alternative splicing, exemplified by phosphorylation-dependent control of CD45 splicing in T-cell activation [UniProt annotation]. Beyond splicing, SFPQ participates in transcriptional regulation through histone deacetylase recruitment and circadian clock repression, and contributes to DNA double-strand break repair and V(D)J recombination via NHEJ pathways 2. SFPQ assembles into nuclear paraspeckles alongside NONO and long noncoding RNA NEAT1, where it sequesters A-to-I edited RNAs 3. Clinically, SFPQ dysregulation drives multiple cancers: upregulation suppresses TGF-β tumor-suppressive signaling through phase-separated condensates that sequester Smad4 4, while SFPQ-TFE3 fusion proteins promote aggressive epithelioid tumors with lineage plasticity through mTORC1 activation 5. In neurodegeneration, SFPQ aggregation alongside edited RNA accumulates in Parkinson's disease and dementia with Lewy bodies nuclei, creating self-propagating pathological inclusions 6. Small-molecule inhibitors targeting NONO similarly suppress cancer-relevant transcription networks 7.