The ESCRT (endosomal sorting complex required for transport) machinery is known 
to sort ubiquitinated transmembrane proteins into vesicles that bud into the 
lumen of multivesicular bodies (MVBs). Although the ESCRTs themselves are 
ubiquitinated they are excluded from the intraluminal vesicles and recycle back 
to the cytoplasm for further rounds of sorting. To obtain insights into the 
rules that distinguish ESCRT machinery from cargo we analyzed the trafficking of 
artificial ESCRT-like protein fusions. These studies showed that lowering 
ESCRT-binding affinity converts a protein from behaving like ESCRT machinery 
into cargo of the MVB pathway, highlighting the close relationship between 
machinery and the cargoes they sort. Furthermore, our findings give insights 
into the targeting of soluble proteins into the MVB pathway and show that 
binding to any of the ESCRTs can mediate ubiquitin-independent MVB sorting.