PRPF40B is a splicing regulatory factor that functions as a repressor of alternative exon inclusion, primarily affecting genes with A-rich intronic motifs and weak 5' splice sites 1. As a mammalian ortholog of the yeast U1 snRNP-associated factor Prp40, PRPF40B interacts directly with splicing factors SF1 and U2AF65, and localizes to nuclear speckles where it modulates alternative splice site selection 2. Notably, PRPF40B regulates NTRK2 alternative splicing to promote production of the full-length TRKB receptor isoform, which is critical for neuronal differentiation and synaptic plasticity 3. In hematologic malignancies, PRPF40B mutations are recurrent in myelodysplastic syndromes and acute myeloid leukemia, where reduced PRPF40B expression is associated with leukemogenesis 1 4. Loss of PRPF40B activates hypoxia-responsive gene signatures and iron metabolism pathways in myeloid cells, suggesting a role in repressing pro-leukemic processes 1. Beyond blood disorders, PRPF40B regulates circMAN1A2 to control glioblastoma ferroptosis and temozolomide sensitivity 5. These findings establish PRPF40B as a multifunctional splicing factor with disease relevance across hematologic and neurologic contexts.