ZCRB1 (zinc finger CCHC-type and RNA binding motif containing 1) is a core component of the U12 mono-snRNP minor spliceosome that regulates splicing of the ~0.5% of human introns processed by this pathway 1. The protein contains both RNA-binding and CCHC zinc finger motifs characteristic of nucleic acid-binding proteins 2. Functionally, ZCRB1 mediates U12-type intron splicing; its depletion causes dysregulation of minor intron-containing genes, particularly those involved in ciliogenesis, while upregulating WNT signaling 1. ZCRB1 recruitment to the minor spliceosome is enhanced by bktRNA1-mediated U12 snRNA methylation 3. Clinically, ZCRB1 expression is dysregulated in multiple cancers: elevated in hepatocellular carcinoma where it promotes malignant progression through USP21 splicing regulation 4, head and neck squamous cell carcinoma where it affects DNA damage response splicing 5, and glioblastoma where it suppresses aerobic glycolysis 6. Conversely, ZCRB1 shows reduced expression in gliomas associated with human adenovirus C infection 7. ZCRB1 is conserved across species, with knockdown in zebrafish causing developmental abnormalities and disrupted ciliogenesis 1. These findings establish ZCRB1 as a critical splicing regulator with significant roles in development and cancer progression.