HUPO Chromosome-Centric Human Proteome Project (C-HPP) has recently published its 4th Special Issue of the Journal of Proteome Research (http://pubs.acs.org/toc/jprobs/15/11) which carries a total of 18 papers. This special issue highlights the progress on the C-HPP and its related projects in many aspects such as HPP Mass Spectrometry Data Interpretation Guidelines, 2016 HPP Metrics, Discovery of 267 Missing Proteins (currently 2930 proteins) and other biological aspects of newly identified proteins encoded by human chromosomes.