PUF60 is a multifunctional RNA-binding protein that plays critical roles in pre-mRNA splicing, cell cycle regulation, and cancer progression. The protein promotes alternative splicing by binding to pyrimidine tracts and 3'-splice sites of pre-mRNAs, particularly those involved in cell cycle control 1. PUF60 regulates the splicing of key cell cycle genes including CDC25C, where its knockdown leads to exon skipping and subsequent nonsense-mediated decay, ultimately inhibiting G2/M transition and cell proliferation 1. In cancer contexts, PUF60 functions as an oncogenic factor - it is overexpressed in lung adenocarcinoma and correlates with poor prognosis 1. The protein drives cancer progression by ensuring proper exon inclusion in proliferation-associated transcripts, and disruption of its RNA-binding activity induces apoptosis in cancer cells 2. Beyond cancer, PUF60 haploinsufficiency causes Verheij syndrome, a neurodevelopmental disorder characterized by growth retardation, intellectual disability, cardiac anomalies, and ocular coloboma 34. The syndrome results from de novo pathogenic variants in PUF60, though inherited cases have been reported 3. PUF60 has also been identified as a novel gene associated with developmental and epileptic encephalopathy with spike-wave activation in sleep 5.