LUC7L3 (LUC7 like 3 pre-mRNA splicing factor) is an RNA-binding protein that plays essential roles in pre-mRNA splicing and genome stability maintenance. As a component of the U1 small nuclear ribonucleoprotein (snRNP), LUC7L3 functions in splice site recognition and spliceosome assembly 1. The protein is regulated by SRSF1, which promotes LUC7L3 translation, positioning it within a splicing regulatory network 2. LUC7L3 depletion results in severe cellular consequences including R-loop accumulation, DNA replication stress, genomic instability, and defective spindle assembly leading to multinuclear cell formation 2. These effects ultimately cause cell cycle arrest, apoptosis, and senescence, highlighting its critical role in cell proliferation 2. Disease relevance includes involvement in cancer biology, where LUC7L3 is identified as a hub gene in bicalutamide resistance networks in prostate cancer 3, and its translation is promoted by the cancer-associated chaperone TRAP1 in ovarian cancer cells 1. Additionally, LUC7L3 functions as a transcriptional repressor of hepatitis B virus replication by suppressing enhancer II/basal core promoter activity 4. The protein also participates in psoriasis-related splicing regulation, particularly affecting fibronectin isoform production 5.