TXNL4A encodes a thioredoxin-like protein essential for pre-mRNA splicing as a component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes within the spliceosome. The protein participates in both spliceosomal assembly and the catalytic steps of splicing, functioning within the precatalytic spliceosome complex. Biallelic variants in TXNL4A cause Burn-McKeown syndrome, characterized by choanal atresia and distinctive craniofacial features including abnormal ears, eyelid malformations, hearing loss, and cleft palate 1. The majority of affected individuals carry a 34 bp promoter deletion on one allele combined with a loss-of-function variant on the other, resulting in reduced TXNL4A expression 2. Mechanistically, patient-derived neural crest cells—the embryonic cell type critical for craniofacial development—show delayed epithelial-to-mesenchymal transition and widespread mis-splicing in developmental genes, particularly within the Wnt signaling pathway, suggesting how reduced TXNL4A dosage compromises craniofacial morphogenesis 2. Homozygous promoter deletions have also been identified in individuals with isolated choanal atresia 1. Recent evidence from C. elegans demonstrates that reduced TXNL4A levels ameliorate tau pathology and neurodegeneration, with TXNL4A levels decreased in Alzheimer's disease human brain, suggesting potential therapeutic relevance in tauopathies 3. At the cellular level, PQBP1 facilitates nuclear import of TXNL4A through a piggyback mechanism involving karyopherin β2, and mutations disrupting this interaction are associated with X-linked intellectual disability 4.