There are already a number of databases that can annotate alternative transcripts with some of these features (46–48). What sets APPRIS apart from all these databases is that APPRIS provides high-quality annotations that are being used in the annotation of the human genome and that these annotations are used to select a principal isoform for each gene. Principal isoforms are selected based on evolutionary evidence in the form of conserved functional and structural motifs and cross-species conservation. The success of APPRIS is due to the observation that most alternative isoforms lack regions of conserved structure or function, or have exons that are evolving at measurably different rates compared with their principal counterparts. The APPRIS database has been able to identify a principal isoform for the majority of human genes (85%).