APPRIS is currently being used to annotate protein-coding genes by annotators in the GENCODE consortium (14) and the CCDS project (42). Annotations based on APPRIS data are already percolating to many users through these databases. We hope that the APPRIS principal isoforms will become accepted as the standard reference sequence for each gene. We believe that the principal isoforms identified by APPRIS are a significant advance on the current practice of selecting the longest variant as the reference isoform and that they should be used in all automatic genome-wide protocols and large-scale analyses.