Expanding the human proteome with microproteins and peptideins

Van Heesch et al. (2026) report the findings of the TransCODE Consortium in a landmark Nature study that systematically maps protein-level evidence for non-canonical open reading frames (ncORFs) across the human proteome. Analysing 95,520 proteomics experiments, the consortium shows that approximately 25% of 7,264 ncORFs produce detectable peptides, substantially expanding the known human proteome. The authors introduce the concept of “peptideins”, microproteins encoded by ncORFs with indeterminate but potentially functional roles, and develop a new evolutionary analysis framework (ORF relative branch length, ORBL) to assess their conservation. One peptidein derived from the OLMALINC long non-coding RNA is shown to have a pan-essential cellular phenotype, demonstrating that Ribo-seq-guided ncORF discovery translates into biologically meaningful targets.