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.