HNRNPLL is an RNA-binding protein that functions as a master regulator of alternative splicing in lymphocytes and other cell types 1. Its primary function involves regulating splicing of critical genes including PTPRC/CD45, which determines naive versus memory T cell phenotypes through CD45RA to CD45RO switching 12. HNRNPLL operates through direct binding to target mRNAs and regulation of splice site selection, as demonstrated by its cell-type-specific regulatory relationship with PTPRC 3. In lymphocyte development, HNRNPLL controls CD45 isoform splicing downstream of the IKAROS transcription factor, shaping the naive/memory T cell phenotype at thymic and postthymic levels 2. Beyond immune function, HNRNPLL regulates alternative splicing of diverse targets including PPP2R1B in osteogenesis 4 and PD-1 intron retention in T cells 5. In B cells, HNRNPLL is essential for activation and germinal center formation, controlling splicing of epigenetic modifiers like KDM6A and SIRT1 6. Clinically, HNRNPLL dysregulation associates with disease susceptibility; cis-splicing quantitative trait loci effects are enriched in autoimmune and inflammatory disease heritability 3. In colorectal cancer, HNRNPLL stabilizes mRNAs encoding DNA replication proteins, promoting proliferation 7, and protects HNRNPLL from degradation in lung adenocarcinoma under energy stress 8.