HTATSF1 (HIV-1 Tat specific factor 1) is a multifunctional RNA-binding protein that plays critical roles in RNA processing, DNA repair, and cellular differentiation. Its primary function involves controlling embryonic stem cell differentiation by regulating ribosome biogenesis - specifically controlling intron removal from ribosomal protein transcripts and regulating ribosomal RNA transcription and processing in complex with splicing factor SF3B1 1. The protein also functions in homologous recombination DNA repair, where CK2 kinase phosphorylates HTATSF1 at Ser748 to facilitate its interaction with TOPBP1, promoting RAD51 recruitment and HR repair 2. HTATSF1 participates in pre-spliceosome assembly and transcription elongation, with disrupted HTATSF1-SF3B1 interactions linked to oncogenic splicing factor mutations 3. Clinically, the CK2-HTATSF1-TOPBP1 axis is hyperactivated in multiple malignancies and renders breast tumors less responsive to chemotherapy, while loss-of-function mutations increase vulnerability to PARP inhibitors 2. HTATSF1 also exhibits β-arrestin-binding properties through an 'arreSTick' motif, influencing its subcellular localization 4. The gene serves as a stable reference for qPCR normalization in muscular dystrophy studies 5.