Protein sequence alignments have become indispensable for virtually any evolutionary, structural or functional study involving proteins. Modern sequence search and comparison methods combined with rapidly increasing sequence data often can reliably match even distantly related proteins that share little sequence similarity. However, even highly significant matches generally may have incorrectly aligned regions. Therefore when exact residue correspondence is used to transfer biological information from one aligned sequence to another, it is critical to know which alignment regions are reliable and which may contain alignment errors.