Hnrnpll, or heterogeneous nuclear ribonucleoprotein L-like, is a tissue-specific RNA-binding protein. It is a key regulator in post-transcriptional gene regulation, mainly functioning in alternative splicing, RNA stability regulation, and translation regulation. It is involved in pathways related to cell differentiation, lymphocyte homeostasis, and cancer metastasis [3].

In embryonic stem (ES) cells, hnRNPLL depletion leads to sustained expression of ES cell-preferred isoforms, causing a differentiation deficiency and resulting in developmental defects and growth impairment in hnRNPLL-KO mice. This is due to its role in promoting multiple ES cell-preferred exon skipping events during the onset of ES cell differentiation, especially the alternative splicing of Bptf and Tbx3, which is crucial for pluripotency exit [1].

In pancreatic ductal adenocarcinoma (PDAC), hnRNPLL knockdown reduces the short isoform of MYOF (MYOFb) through exon 17 retention of MYOF, inhibiting metastasis, indicating its importance in early PDAC metastasis [2].

In B-cells, while Hnrnpllthu/thu mice show normal B-cell development in the bone marrow, they are deficient in generating germinal center (GC) B cells in response to in vivo immunization. The mutation disrupts hnRNPLL-mediated alternative splicing of the Ptprc gene in plasmablasts, but this does not affect B-cell development and function [4].

In colorectal cancer, knockdown of Hnrnpll enhances colon cancer cell invasion and metastasis ability, as it modulates the alternative splicing of CD44. Also, Hnrnpll promotes cell cycle progression and proliferation of colorectal cancer cells by stabilizing mRNA for DNA replication proteins [5,6].

In summary, hnRNPLL plays essential roles in cell differentiation, lymphocyte homeostasis, and cancer-related processes. Studies using hnRNPLL KO/CKO mouse models have significantly contributed to understanding its functions in embryonic development, cancer metastasis, and lymphocyte-related diseases. These models have provided insights into the underlying molecular mechanisms, highlighting hnRNPLL as a potential therapeutic target in relevant disease areas.