DNAJC8 is a nuclear DnaJ protein (HSP40 family member) with diverse cellular functions spanning protein aggregation suppression, RNA splicing regulation, and metabolic control. As a molecular chaperone, DNAJC8 suppresses polyglutamine aggregation of ATXN3 in neuronal cells through its C-terminal domain, functioning independently of the traditional HSP70-based chaperone machinery 1. In splicing regulation, DNAJC8 serves as a key splicing factor that stabilizes pre-spliceosome assembly during branch site proofreading, working alongside SF1 and SF3A2 to ensure accurate splice site selection 2. The protein also acts as a cochaperone that binds SRPK1 and mediates its interactions with HSP70 and HSP90, thereby regulating SR protein phosphorylation and alternative splicing in response to cellular stress 3. Additionally, DNAJC8 plays a role in cellular metabolism by promoting PKM2 nuclear translocation and glucose uptake, though this function is negatively regulated by TIG1 4. In disease contexts, DNAJC8 shows clinical significance as an upregulated oncogene in hepatocellular carcinoma associated with poor prognosis 5 and as a potential autoantibody target in Alzheimer's disease 6. The protein also provides protective effects against TDP-43 toxicity by retaining it in nuclear liquid phases 7.