CLU and Parkinson disease: CLU directly binds to α-synuclein aggregates and limits their internalization into astrocytes; thus, contributing to the pathogenesis of PD (Filippini et al., 2021), whereas NEDD4 ligase ubiquitinates α-synuclein and clears α-synuclein aggregates via endolysosomal pathway; thereby protecting against α-synuclein-induced progressive neurodegeneration (Tofaris et al., 2011).