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Additional file 1: Contains supplementary figures and tables to give further detail to the methods and results section

Germon et al, (2022) Supplementary files, comprising: A.Supplementary Figures 1 and 2 as a single pdf file. B. Supplementary Table 1. C. Supplementary Table 2.

Additional file 6: Figures S1 and S2. Supplementary figures detailing in Figure S1 the location of deletions in other reported direct RNAseq data and in Figure S2 the MS/MS spectra for the peptide unique to the furing cleavage site deletion variant.

Retromer controls cellular homeostasis through regulating integral membrane protein sorting and transport and by controlling maturation of the endo-lysosomal network. Retromer dysfunction, which is linked to neurodegenerative disorders including Parkinson’s and Alzheimer’s diseases, manifests in complex cellular phenotypes, though the precise nature of this dysfunction, and its relation to neurodegeneration, remain unclear. Here, we perform an integrated multi-omics approach to provide precise insight into the impact of Retromer dysfunction on endo-lysosomal health and homeostasis within a human neuroglioma cell model. We quantify widespread changes to the lysosomal proteome, indicative of broad lysosomal dysfunction and inefficient autophagic lysosome reformation, coupled with a reconfigured cell surface proteome and secretome reflective of increased lysosomal exocytosis. Through this global proteomic approach and parallel transcriptomic analysis, we provide a holistic view of Retromer function in regulating lysosomal homeostasis and emphasise its role in neuroprotection.