## 1 Introduction  
The plasma membrane is a selective barrier for controlled exchanges between eukaryotic cells and their environments. Endocytosis describes the cellular process by which parts of the plasma membrane are invaginated to then pinch off membrane-bound carriers for the uptake of material that originates from the extracellular space or the cell surface [1]. Endocytosis thereby serves a multitude of cellular functions that range from nutrient uptake and growth factor signaling to the dynamic maintenance of specialized areas of the plasma membrane, such as the leading edge of migratory cells or the immunological synapse of lymphocytes. Amongst the endocytic processes that occur in all eukaryotic cells, the clathrin pathway remains by far the best-characterized [2, 3, 4]. Here, the recruitment of clathrin and its adaptors onto cytosolic signals of transmembrane proteins drives the bending of a patch of plasma membrane into a narrow endocytic pit that then detaches by the action of the scission GTPase dynamin to give rise of an endocytic vesicle. It is now well established that narrow endocytic pits can also form in endocytic processes that are not driven by the clathrin machinery [5, 6, 7, 8]. A multitude of cellular proteins are involved in these clathrin-independent endocytosis events, such as small GTPases of the Rho/Rac/Cdc42 [9, 10] and Arf families [11, 12], actin [13, 14], galectins [15, 16], endophilins [17, 18], and reticulon3 [19]. Whether these constitute different endocytic pathways or contribute at different steps to the same endocytic pathway has remained an open question (discussed in Reference [20]). While clathrin-independent endocytic carriers were initially described as pleiomorphic [21], more recent findings identify them in many cases as tubular elements [14; 16; 17; 19; 22]. In the field of clathrin-independent endocytosis research, the key challenge is to explain how cargo proteins are recruited and the plasma membrane is bent to form endocytic pits without the help of the clathrin coat. It is indeed another common characteristic of clathrin-independent endocytic processes that highly organized electron dense protein assemblies (termed coats) cannot be found at sites of endocytic pit formation. According to the GlycoLipid-Lectin (GL-Lect) hypothesis, oligomeric sugar-binding proteins (lectins) from pathogens or of cellular origin (notably galectins) interact with glycosylated lipids (glycosphingolipids (GSLs) or glycosylphosphatidyl!inositol (GPI)-anchored proteins) in a way such as to drive narrow membrane bending. This leads to the formation of tubular endocytic pits from which so-called clathrin-independent carriers detach for the cellular uptake of pathogens (e.g., Shiga and cholera toxins, polyomaviruses, norovirus, etc. ), or cellular glycoproteins (e.g., integrins, CD44, etc.) that are recruited by galectins [23; 24; 25; 26] (Figure 1). To what extent the GL-Lect hypothesis provides the conceptual framework for a unifying view on clathrin-independent endocytosis remains to be established. Once internalized, proteins and lipids are sorted to three principal destinations within the endocytic pathway: (i) late endosomes and lysosomes for degradation and nutrient uptake [27]; (ii) back to the plasma membrane for recycling [28]; and (iii) retrograde transport to the Golgi apparatus for subsequent polarized secretion to specialized areas of the plasma membrane, such as the leading edge of migratory cells or the immunological synapse of lymphocytes [29], or further retrograde trafficking to the endoplasmic reticulum (ER) for retro-translocation to the cytosol [30]. For a discussion of the molecular signals that determine sorting on endosomes the reader is referred to excellent recent reviews [31; 32; 33]. In the context of the GL-Lect hypothesis, many key questions arise on regulation, structural organization, and physiological functions.