The preservation of a healthy proteome is important for all cellular function. Sequential protein quality control (QC) mechanisms along the endocytic pathway safeguard the identity of different organelles by eliminating damaged or mislocalized proteins. In Saccharomyces cerevisiae, the Rsp5 ubiquitin ligase is required for cargo ubiquitination at all steps of endocytic QC, and its activity is mediated by its recruitment to organelle membranes by specific adaptors. The ART adaptor network directs Rsp5 to the plasma membrane (PM), while the intracellular adaptor Ssh4 recruits it to the vacuole membrane (VM). This study shows that PM proteins mistargeted to the VM are recognized and sorted by the Ssh4-Rsp5 complex and that Ssh4 contains important features that facilitate its cargo sorting. Furthermore, Ssh4-Rsp5-mediated QC employs a seemingly promiscuous mechanism of cargo recognition at the VM. Finally, targeting Ssh4 to the PM induces some non-specific degradation of PM proteins that are accessible to Ssh4-Rsp5.