PipeAlign2 is a protein family analysis tool integrating a multi-step process ranging from the search for sequence homologues in protein and 3D structure databases to the structural / functional annotation of the family. The complete, automatic pipeline takes a single sequence or a set of sequences as input and constructs a high-quality, validated multiple sequence alignment (MSA) in which sequences are clustered into potential functional subgroups. Sequence annotations are automatically extracted from the public database (Uniprot, InterPro, etc.), cross-validated and integrated in the MSA. For the more experienced user, the PipeAlign2 server also provides numerous options to run only a part of the analysis, with the possibility to modify the default parameters of each step.