CRNKL1 is a protein-coding gene that has been implicated in multiple biological processes and disease-related pathways. It is a highly selective regulator involved in the nuclear retention of intron-retaining HIV-1 and certain cellular mRNAs. This regulation of cytoplasmic levels of these mRNAs is a novel cellular mechanism, which HIV-1 may have exploited to direct its complex splicing pattern [1].

In esophageal adenocarcinoma, CRNKL1 was identified as a prognostic biomarker through differential co-expression and expression analysis. It could effectively stratify patients into high-risk and low-risk groups, outperforming traditional biomarkers [2].

In bladder cancer, cigarette smoking combined with the A allele of rs2273058 in CRNKL1 increased the cancer risk. Mechanistically, this allele promoted CRNKL1 expression, which may accelerate cell cycle and proliferation [3].

In esophageal cancer, multi-omics analysis identified CRNKL1 as a hub splicing factor, and its target genes and pathways were related to cancer stemness and metastasis [4].

In conclusion, CRNKL1 plays a significant role in regulating the cytoplasmic levels of intron-retaining mRNAs, which is relevant to the replication of HIV-1. Additionally, it has potential as a prognostic biomarker and is involved in the development of several cancers, including esophageal adenocarcinoma, bladder cancer, and esophageal cancer. The study of CRNKL1 in these contexts provides insights into disease mechanisms and potential therapeutic targets.