DNAJC17 is a heat shock protein (HSP40) family member, identified in mouse as 
susceptibility gene for congenital hypothyroidism. DNAJC17 knockout mouse 
embryos die prior to implantation. In humans, germline homozygous mutations in 
DNAJC17 have been found in syndromic retinal dystrophy patients, while 
heterozygous mutations represent candidate pathogenic events for 
myeloproliferative disorders. Despite widespread expression and involvement in 
human diseases, DNAJC17 function is still poorly understood. Herein, we have 
investigated its function through high-throughput transcriptomic and proteomic 
approaches. DNAJC17-depleted cells transcriptome highlighted genes involved in 
general functional categories, mainly related to gene expression. Conversely, 
DNAJC17 interactome can be classified in very specific functional networks, with 
the most enriched one including proteins involved in splicing. Furthermore, 
several splicing-related interactors, were independently validated by 
co-immunoprecipitation and in vivo co-localization. Accordingly, co-localization 
of DNAJC17 with SC35, a marker of nuclear speckles, further supported its 
interaction with spliceosomal components. Lastly, DNAJC17 up-regulation enhanced 
splicing efficiency of minigene reporter in live cells, while its knockdown 
induced perturbations of splicing efficiency at whole genome level, as 
demonstrated by specific analysis of RNAseq data. In conclusion, our study 
strongly suggests a role of DNAJC17 in splicing-related processes and provides 
support to its recognized essential function in early development.