ESS2 (ess-2 spliceosome associated protein), also known as DGCR14, is a nuclear protein that functions as both a transcriptional coregulator and spliceosome component 1. The protein contains a conserved coiled-coil structure and is involved in pre-mRNA splicing through its association with spliceosomal C and C* complexes 1. ESS2 bridges transcriptional regulators and spliceosomal complexes via distinct domains - its N-terminal region (1-200 aa) associates with transcription factors like RORγ/γt, while its C-terminal region is required for snRNA interactions 2. The protein associates with U1, U4, and U6 snRNAs and is phosphorylated by CDK11 as part of spliceosome regulation 23. ESS2 is located in the 22q11.2 deletion syndrome region and plays critical roles in cell differentiation, proliferation, and T-cell survival through regulation of Myc and IL-7 signaling pathways 41. ESS2 knockout mice exhibit embryonic lethality, and the gene has been implicated in cancer progression, particularly prostate cancer, where it controls chr22 remodeling through CHD1 recruitment 5. Rare variants in ESS2 have also been associated with increased suicide risk 6.