PUS7L (pseudouridine synthase 7 like) is a pseudouridine synthase that catalyzes pseudouridylation of mRNAs and tRNAs. It functions as a stand-alone PUS enzyme that introduces pseudouridine (Ψ) modifications at specific sites in human tRNAs during pre-tRNA processing 1. The enzyme localizes to the nucleus where it performs pseudouridine synthesis activity [annotation supported by GO terms]. Regarding disease relevance, PUS7L has been implicated in several pathological conditions. In sepsis, elevated PUS7L phosphopeptides and increased precursor intensity were detected in plasma samples from ICU-sepsis patients compared to controls 2. In colorectal cancer, PUS7L expression levels correlate with significant differences in pseudouridine distribution between tumor and normal tissues, with distinct Ψ levels in snoRNAs serving as potential tumor biomarkers 3. Additionally, rare variants in PUS7L were associated with age-related hearing loss in a large genetic association study 4. Clinically, PUS7L represents a potential therapeutic target and biomarker in cancer and age-related conditions. The identification of specific RNA targets modified by PUS7L 1 provides mechanistic insights into how pseudouridine modifications contribute to disease pathogenesis, though functional studies are needed to establish causality in these disease contexts.