Aside from the idea that reduced ribosome levels alter translation directly and are predominantly responsible for human DBA (Mills and Green, 2017; Khajuria et al., 2018), two recent studies propose that degradation of excess orphan Rp suppresses proteasome and autophagic flux in Drosophila Rp mutants, leading to protein aggregation and proteotoxic stress. Here, BLOC1S3 is linked to Diamond-Blackfan anemia.