MFAP1 (microfibril-associated protein 1) functions as a dual-role protein in both extracellular matrix organization and pre-mRNA splicing. As an ECM component, MFAP1 is ubiquitously expressed and participates in microfibril assembly and tissue homeostasis 1. In the nucleus, MFAP1 serves as a spliceosomal B complex protein where it forms a 5' exon binding channel with UBL5, stabilizing pre-mRNA splice site recognition 2. MFAP1 also functions as a nuclear speckle-associated protein whose expression levels modulate nuclear speckle size, stability, and dynamics 3. Mechanistically, MFAP1 depletion impairs splicing globally and reduces expression of DNA damage response genes, indirectly affecting genome integrity independent of transcription or R-loops 4. Clinically, MFAP1 is required for androgen receptor variant (AR-V) synthesis in castration-resistant prostate cancer; its depletion reduces AR-V abundance and sensitizes cancer cells to ionizing radiation, suggesting therapeutic potential 5. MFAP1 expression changes significantly with age across multiple tissues 6. Although localized to chromosome 15-q21, near the Marfan syndrome locus, MFAP1 mutations are not associated with Marfan syndrome 7.