ProtPhylo is a web server to retrieve phenotype-to-protein (Phenotype Phylogenetic Profiling) and protein-to-protein (Protein Phylogenetic Profiling) functional associations based on comparative genomics analysis of 2048 complete genomes (1678 bacteria, 255 eukaryotes and 115 archea). ProtPhylo will search for proteins with shared evolutionary history to either a phenotype or a protein of interest within a user-defined organism. Then it proceeds to construct a phylogenetic matrix based on user-defined orthologous relationships and rank phylogenetic neighbors of the query protein or the phenotypic property based on the Hamming distance. Subset of co-evolving proteins (phylogenetic neighbors) can be further prioritized based on combined information from datasets on subcellular localization, protein domains and membrane spanning regions. The resulting protein list can be exported into a csv text file for further analyses. Please refer to the paper published in 2015 NAR Web server issue (Nucleic Acids Res. 2015 Jul 1;43(W1):W160-8) for details.