ZBTB8OS (also known as archease) is a cofactor essential for activating RTCB, the catalytic subunit of the tRNA-splicing ligase complex involved in pre-tRNA maturation 1. ZBTB8OS catalyzes GTP-dependent activation of RTCB, facilitating the formation of an RTCB-guanylate intermediate required for RNA ligation 1. The protein functions in two distinct RNA splicing pathways: canonical tRNA splicing and non-canonical XBP1 mRNA splicing. In tRNA maturation, ZBTB8OS enables ligation of exon halves generated after intron removal by the tRNA-splicing endonuclease 1. During endoplasmic reticulum (ER) stress, ZBTB8OS is required for XBP1 mRNA splicing via the unfolded protein response (UPR), where it cooperates with RTCB to ligate exon ends after IRE1/ERN1-mediated intron removal 2. This XBP1 splicing generates the active XBP1s transcription factor, which induces genes resolving protein folding defects 2. Structurally, ZBTB8OS contains an extended N-terminal domain and a compacted C-terminal domain that interact with and stabilize RTCB in cells 3. Loss of ZBTB8OS function impairs antibody secretion in plasma cells and represents a potential therapeutic target for diseases involving elevated XBP1s expression 2.