RNPC3 (RNA binding region containing 3) is a nuclear protein encoding two RNA recognition motifs (RRM) that functions as a critical component of the minor spliceosome 1. It binds to the 3'-stem-loop of U12 snRNA and catalyzes U12-dependent splicing of minor introns, which comprise less than 1% of non-coding sequences but are essential for ~700 genes (0.35% of the human genome) 2. RNPC3 extends its regulatory role beyond splicing: it interacts with ANKRD11 to facilitate HDAC3-mediated histone deacetylation at H3K9 and H4K5, thereby regulating gene expression through coupled splicing-histone modification mechanisms 3. Pathogenic biallelic RNPC3 variants cause congenital hypopituitarism with pituitary hypoplasia and variable hormone deficiencies (growth hormone, prolactin, thyrotropin) 45. Notably, affected females develop primary ovarian insufficiency, suggesting female-specific gonadal vulnerability 4. Additional features include developmental delay, neuropathy, and congenital cataracts 5. Clinically, RNPC3 dysfunction is associated with systemic sclerosis serology 6. Conversely, minor spliceosome inhibition via RNPC3 downregulation restricts cancer cell proliferation through replication stress and p53-dependent apoptosis 2, suggesting therapeutic potential.