The 2025 Report on the Human Proteome from the HUPO Human Proteome Project

The HUPO Human Proteome Project (HPP) aims to complete the human protein parts list by detecting evidence of expression and of function for all proteins in the human proteome, and make proteomics an integral part of multiomics studies of health and disease. Here we describe the state of the 2025 HPP reference proteome of 19,435 proteins, based on GENCODE v48, UniProtKB 2025_03, Human Protein Atlas 24, MassIVE-KB 2023, and PeptideAtlas 2025-01. We evaluate the progress in the past year, with 93.6% of the proteome detected, and examine the proteins that have not yet been detected to determine where further progress can be made. We also evaluate the progress in determining at least one function for every protein in the HPP target list, finding an increase of 288 proteins in the highest category (FE1) to 5562. Finally, we provide highlights from 12 Biology/Disease-based HPP initiatives, HPP resource pillars, and π-HuB.