Nonphototrophic hypocotyl 3 domain proteins: traffic directors, hitchhikers, or both?

The nonphototrophic hypocotyl 3 (NPH3) domain is plant specific and of unknown function. It is nearly always attached to an N-terminal BTB domain and a largely unstructured C-terminal region. Recent reports revealed NPH3-domain GTPase activity and connection to intracellular trafficking, condensate formation, membrane attachment of the C-terminal region for some NPH3-domain proteins and, at the physiological level, drought-related function for at least one NPH3-domain protein. We integrate these new ideas of NPH3-domain protein function into two, nonexclusive, working models: the 'traffic director' model, whereby NPH3-domain proteins regulate intracellular trafficking and, the 'hitchhiker' model whereby NPH3-domain proteins ride the trafficking system to find ubiquitination targets. Determining which model best applies to uncharacterized NPH3-domain proteins will contribute to understanding intracellular trafficking and environmental responses.