THOC6 (THO complex subunit 6) is a critical component of the Transcription Export (TREX) complex that facilitates mRNA processing and nuclear export in mammalian cells 1. THOC6 is essential for TREX tetramer formation, composed of four six-subunit THO monomers, which supports mammalian-specific RNA processing functions beyond the nuclear export functions conserved in yeast 1. The protein enables proper mRNA splicing in neural tissue and regulates key signaling pathways during human corticogenesis that control the transition from proliferative to neurogenic divisions 1. Biallelic loss-of-function variants in THOC6 cause Beaulieu-Boycott-Innes syndrome (BBIS), an autosomal recessive neurodevelopmental disorder characterized by moderate to severe intellectual disability, facial dysmorphisms, and multiple congenital malformations affecting cardiac, skeletal, renal, and genitourinary systems 23. Mechanistically, THOC6 variants reduce ALYREF binding affinity to THOC5, impairing TREX tetramer formation and resulting in mRNA mis-splicing rather than nuclear export defects 1. Additionally, THOC6 regulates bone homeostasis by mediating RUNX2 ubiquitination in osteoblast differentiation 4. The protein has also been identified as a potential biomarker in glioma 5.