SQSTM1 is a universal cargo receptor that is involved in multiple types of autophagy. It aggregates or recruits ubiquitylated protein inclusion bodies to autophagosomes for degradation, and mutations in SQSTM1 are linked to numerous neuropathologies. The HECT E3 ubiquitin ligase family member NEDD4 interacts with the autophagy protein LC3 and is required for rapamycin-induced activation of autophagy. NEDD4 was previously shown to ubiquitylate SQSTM1 and, on page 3839, Wannian Yang, Qiong Lin and colleagues further characterise the role of SQSTM1 in autophagy. They find that NEDD4 interacts with and ubiquitylates SQSTM1 in its PB1 domain, which has a function in homo- or hetero-dimerisation of SQSTM1. Interestingly, the polyubiquitylation of SQSTM1 occurs through conjugation at residue K63 and does not cause proteasomal degradation of SQSTM1. Furthermore, the authors show that knockdown of NEDD4 leads to the accumulation of inclusion bodies that contain SQSTM1 and that the ubiquitylation of SQSTM1 is required for its function in inclusion body autophagy. This work highlights NEDD4 as a key E3 ubiquitin ligase for the autophagy receptor SQSTM1, whose misregulation is, among others, associated with Parkinson's, Huntington's and Alzheimer's disease.