LAUSR

As of the first week of April 2023, according to the data from the UniProt Knowledgebase (https://www.uniprot.org) (UniProt Consortium, 2023), the human proteome has a record of 20,422 canonical as well as 21,998 non-canonical protein isoforms. These figures are noteworthy because the number of non-canonical isoforms is almost equal to the number of canonical ones, suggesting that “non-canonical” isoforms may be equally important as their canonical counterparts. Despite the fact that scientists have studied canonical isoforms in greater detail over the years, there are still hundreds to thousands of uncharacterized canonical and non-canonical isoforms as their biological functions are yet to be revealed. Besides, the discovery of protein encoding ncRNAs (Jackson et al., 2018) has added another layer of complexity to the situation, and as such, the current reported total number of human proteoforms (Smith and Kelleher, 2018) is likely to be underestimated. The Research Topic titled “Characterizing the uncharacterized human proteins” showcases the latest discoveries in the field of unstudied or under-studied proteins/isoforms. It consists of 9 published manuscripts, including 6 research and 3 review articles, with 66 different contributors. This Research Topic covers a wide range of studies, from individual uncharacterized proteins to high-throughput analyses of novel peptides/protein variants in both normal and pathological conditions. Among the research works covered in this Research Topic, Tan et al. unveiled the potential relationships between essential micronutrients and uncharacterized human proteins C9orf85 and CXorf38, where their expressions could be selectively induced by manganese and selenium. Dong et al. demonstrated that Max interacting protein 1–0 (Mxi1-0), a functional isoform of Mxi1, potentiates hypoxic pulmonary hypertension through MEK/ERK/c-Myc-mediated proliferation of pulmonary arterial smooth muscle cells. Tian et al. reported on a human case carrying two rare variants of ARHGAP31 [c.2623G>A (p.Glu875Lys)] and FBLN1 [c.1649G>A (p.Arg550His)], where the synergistic effects of these two protein mutants may potentiate the terminal transverse limb defects (TTLD), expanding the clinical complexity of mutant gene product interactions in genetic disorders. Zhang et al. studied arrestin domain containing 2 (ARRDC2), a protein in the α-arrestin family, in ovarian cancer OPEN ACCESS