C2orf49, also known as ASW (Archease Subunit of tRNA splicing Ligase), is an accessory subunit of the tRNA-splicing ligase complex essential for tRNA maturation 1. It functions as a component of the mammalian RNA ligation machinery, where it cooperates with RTCB (the catalytic subunit), archease, and DDX1 helicase to join spliced tRNA halves by forming canonical 3',5'-phosphodiester bonds at the splice junction 1. The protein localizes to the nucleus and nucleoplasm, where it participates in the generation of functional tRNAs required for protein synthesis 1. Beyond tRNA splicing, C2orf49 may possess broader RNA ligase activity toward other RNA substrates. Developmental studies indicate C2orf49 orthologs regulate cell survival and anteroposterior patterning, with dysregulated expression triggering apoptosis 2. Clinically, the C2orf49-derived long non-coding RNA C2orf49-DT is upregulated in colorectal cancer samples and associated with poor patient prognosis, correlating with increased cell proliferation pathways and proposed as a potential biomarker for cancer diagnosis and prognostication 3. These findings suggest C2orf49 dysfunction may contribute to both developmental abnormalities and oncogenic transformation.