Updated project metadata. A superfamily of invariant surface glycoproteins (ISGs) populates the African trypanosome surface, one of which, ISG75, is implicated in uptake of the century-old drug suramin. We disrupted the ISG75 gene locus encoding an array of six ISG75 paralogs on chromosome V by CRISPR/Cas9 knockout. Here we characterise this knockout strain by quantitative whole cell proteomics. Additionally, we analyse the way ISG75 knockout cells respond to suramin on the proteome level.