Highlights d A proteomic approach to identify CRL substrates ubiquitylated at cellular membranes d The ER shaping protein Lunapark is ubiquitylated by the CRL3 KLHL12 ubiquitin ligase d Lunapark binds mTOR and its ubiquitylation affects lysosomal recruitment of mTORC1 d Inhibition of Lunapark ubiquitylation leads to neurodevelopmental defects
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