The DNAJ/HSP40 family represents a heterogeneous group of co-chaperones characterized by the presence of the remarkably conserved J-domain, responsible for the regulation of the ATPase activity of HSP70s 1,2,3,4. Based on their architecture, DNAJs/HSP40s are classified in three main subtypes/subfamilies. DNAJs/HSP40s are homodimeric proteins residing in the cytosol of prokaryotes and various subcellular compartments of eukaryotes as well as in the extracellular milieu 5,6,7,8,9,10. They play essential roles in gene expression and translational initiation, folding and unfolding as well as translocation and degradation of proteins. DNAJs/HSP40s bind to unfolded or non-native polypeptides in order to prevent their aggregation 5. Folded proteins are also clients of DNAJs/HSP40s. Their binding mediates the “remodeling” of large multiprotein complexes impacting the balance of protein/protein interactions 7. DNAJs/HSP40s are implicated in various human diseases including microbial infections 11, autoimmune diseases 12,13,14,15, neurodegenerative disorders 16, 17, and cancer 18. Herein, the diversity of the DNAJ/HSP40 family and its role in disease and therapy is compiled.