XAB2 (XPA binding protein 2) is a multifunctional protein that serves as a critical component of the spliceosome, participating in pre-mRNA splicing through its association with the Prp19 complex 1 2. The protein contains multiple tetratricopeptide repeat (TPR) motifs, with TPR motifs 2-4 and 11 being essential for its splicing function through interaction with SNW1 1. XAB2 plays a crucial role in maintaining global transcription by regulating POLR2A expression; its depletion causes severe splicing defects in POLR2A with intron retention, leading to reduced RNA polymerase II levels and impaired transcription 1. Beyond splicing, XAB2 is essential for DNA damage repair, specifically in transcription-coupled nucleotide excision repair (TC-NER) where it facilitates DNA damage recognition by promoting RNA polymerase II release from UV lesions 2. The protein also promotes homologous recombination by mediating end resection of DNA double-strand breaks and Ku protein eviction, operating independently of the ATM kinase pathway 3 4. XAB2 deficiency leads to cellular senescence through p53/p21 upregulation and has been implicated in cancer chemoresistance, where it enhances DNA repair capacity and promotes oxaliplatin resistance in colorectal cancer 1 5.