CRNKL1 (crooked neck pre-mRNA splicing factor 1) is a component of the spliceosome machinery that plays critical roles in pre-mRNA splicing regulation and nuclear RNA retention. As part of the Prp19-associated complex, CRNKL1 is involved in both major and minor spliceosome-mediated splicing processes 1. A key function of CRNKL1 is the selective regulation of nuclear export for intron-retaining mRNAs, including HIV-1 unspliced transcripts and specific cellular mRNAs, effectively acting as a nuclear retention factor 1. Recent studies have identified CRNKL1 as essential for normal brain development, with pathogenic variants causing severe microcephaly, pontocerebellar hypoplasia, and seizures 2. The protein demonstrates tissue-specific regulatory functions despite its involvement in the ubiquitous splicing process. CRNKL1 dysregulation has significant clinical implications, serving as a prognostic biomarker in esophageal adenocarcinoma with high predictive accuracy 3. Environmental toxins like TCDD can alter CRNKL1 expression, contributing to splicing dysregulation 4. Additionally, genetic variants in CRNKL1 combined with cigarette smoking increase bladder cancer risk through m6A-mediated expression changes 5. These findings establish CRNKL1 as both a fundamental splicing regulator and a clinically relevant therapeutic target in multiple disease contexts.