Rab GTPases have been identified more than 20 years ago, and their central role as regulators of
protein trafficking has attracted considerable attention to this protein family. Hundreds of Rabs have been
described in the literature based on bioinformatics analysis, but only a small proportion has been
experimentally characterized. Using the human Rab family as an example, we discuss here how our
knowledge of the Rab universe is biased towards evolutionarily older, more highly and widely expressed
proteins. Newly described Rab proteins have thus received little attention. We explore the types of
functional and structural novelty that newly characterized Rabs are unveiling, and discuss the importance of
these poorly characterized proteins by exploring their participation in human disease.
Keywords: Rab, Evolution, Novelty, Conservation, Expression.
