Abstract
There is good evidence that, in addition to the canonical clathrin-associated endocytic machinery, mammalian cells possess multiple sets of proteins that are capable of mediating the formation of endocytic vesicles. The identity, mechanistic properties and function of these clathrin-independent endocytic pathways are currently under investigation. This Commentary briefly recounts how the field of clathrin-independent endocytosis has developed to date. It then highlights recent progress in identifying key proteins that might define alternative types of endocytosis. These proteins include CtBP (also known as BARS), flotillins (also known as reggies) and GRAF1. We argue that a combination of information about pathway-specific proteins and the ultrastructure of endocytic invaginations provides a means of beginning to classify endocytic pathways.