The unexplainable plasma protein measurements from Proximity Extension Assays

<jats:p>Plasma proteomics assays aim to capture biologically interpretable circulating protein signals. Here we systematically assess Olink Explore targets with exceptionally low variance explainability by integrating genetic associations, cross-platform concordance and tissue and peptide atlases. We identify a subset of protein targets likely lacking robust plasma signals, highlighting assay- and tissue-specific limitations with implications for panel design, statistical power and interpretation of large-scale proteomics studies.</jats:p>