Eukaryotic cells deftly coordinate an array of endocytic pathways beyond the classical clathrin-mediated endocytic route. Although the existence of clathrin-independent endocytic pathways has been accepted for some time, only recently have tools been developed that specifically delineate their fine details, including molecular composition and ultrastructural morphology. Identification of the salient features of distinct pathways has concomitantly attributed them with specific roles during important cellular processes. Insight from model organisms confirms these roles and suggests maintenance of crucially adapted functions across species. Among other roles, clathrin-independent endocytosis has now been linked to plasma membrane repair, cellular spreading, cellular polarization, and modulation of intercellular signaling. The field is now primed to identify how these pathways function within physiologically relevant environments.
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