PRPF40A is a spliceosomal component that functions primarily as a regulator of pre-mRNA splicing with specialized roles in exon inclusion. In myeloid cells, PRPF40A acts as an activator of cassette exon inclusion, particularly for exons flanked by short, GC-rich introns localized to nuclear speckles 1. PRPF40A is globally required for microexon splicing (exons ≤30 nt) in neuronal cells, where it coregulates microexons with SRRM4 in a size-dependent manner 2. Mechanistically, PRPF40A contains tandem WW domains that recognize proline-rich motifs in spliceosomal proteins SF1 and SF3A1, promoting early spliceosome assembly and bridging 5' and 3' splice site recognition 3. An intramolecular autoinhibitory mechanism within PRPF40A enhances binding selectivity for high-affinity partners. Beyond splicing, PRPF40A knockdown increases myeloid cell death and reduces proliferation 1. Clinically, PRPF40A expression correlates with hypoxia markers in non-small cell lung cancer 4 and associates with overall survival in mantle cell lymphoma 5. PRPF40A is also implicated in pediatric acute myeloid leukemia pathogenesis as a hub gene regulated by miR-133 6.