Functional domains within DNAJC21 are disrupted by homozygous mutations in individuals with the clinical bone marrow failure SDS. The J domain at the extreme N-terminus mediates interaction with heat shock protein 70 to stimulate its ATPase activity and is likely disrupted within its critical H-P-D motif by the P32A and K34E missense mutations. Nonsense mutations encoding premature stop codons are likely to result in nonsense-mediated decay of messenger RNA, and frameshift mutations caused by splicing mutations truncate the protein before the predicted C-terminal zinc finger domains. Professional illustration by Patrick Lane, ScEYEnce Studios.