Luc7l2, a paralog of the yeast U1 small nuclear RNA (snRNA)-associated splicing factor Luc7p, is involved in pre-mRNA splicing regulation. It is associated with multiple biological pathways such as energy metabolism, DNA damage repair, and innate immune response, and is of great biological importance in various physiological and pathological processes [6].

In glioblastoma, histone H3K9 lactylation activates LUC7L2 transcription. LUC7L2 then mediates intron 7 retention of MLH1, reducing MLH1 expression, inhibiting mismatch repair, and conferring temozolomide resistance [1]. In liver cancer cells, LUC7L2 promotes proliferation by enhancing DNA damage repair via RRAS [3]. In nasopharyngeal carcinoma, LUC7L2 promotes radioresistance through autophagy, and high LUC7L2 expression is associated with shorter survival in patients [5]. Loss of LUC7L2 shifts energy metabolism from glycolysis to OXPHOS by multiple splicing-related mechanisms [2]. Also, LUC7L2 negatively regulates the innate antiviral response by mediating MITA/STING intron retention [4].

In conclusion, Luc7l2 is crucial in pre-mRNA splicing and significantly impacts multiple disease-related processes such as drug resistance in glioblastoma, proliferation in liver cancer, radioresistance in nasopharyngeal carcinoma, energy metabolism regulation, and innate antiviral response. Studies, including those potentially using KO/CKO mouse models (although not explicitly detailed in all references), have enhanced our understanding of its role in these disease areas, providing potential therapeutic targets.