Functions as a co-chaperone, regulating the substrate binding and activating the ATPase activity of chaperones of the HSP70/heat shock protein 70 family (PubMed:7957263, PubMed:22219199). In parallel, also contributes to the ubiquitin-dependent proteasomal degradation of misfolded proteins (PubMed:15936278, PubMed:21625540). Thereby, may regulate the aggregation and promote the functional recovery of misfolded proteins like HTT, MC4R, PRKN, RHO and SOD1 and be crucial for many biological processes (PubMed:12754272, PubMed:20889486, PubMed:21719532, PubMed:22396390, PubMed:24023695). Isoform 1 which is localized to the endoplasmic reticulum membranes may specifically function in ER-associated protein degradation of misfolded proteins (PubMed:15936278). Interacts with HSP70 (HSPA1A or HSPA1B) (PubMed:21625540, PubMed:22219199). Interacts with HSPA8/Hsc70 (PubMed:15936278). Interacts with PSMA3 and most probably with the whole proteasomal complex (PubMed:15936278). More abundantly expressed in neocortex, cerebellum, spinal cord and retina where it is expressed by neuronal cells (at protein level) (PubMed:1599432, PubMed:12754272). Detected at much lower level in non-neuronal tissues including kidney, lung, heart, skeletal muscle, spleen and testis (at protein level) (PubMed:12754272, PubMed:1599432). Isoform 1 is more abundant in neocortex and cerebellum compared to isoform 2 (at protein level) (PubMed:12754272). The J domain is sufficient to interact with HSP70 (HSPA1A or HSPA1B) and activate its ATPase activity (PubMed:22219199). The J domain is also required for the HSP70-mediated and ubiquitin-dependent proteasomal degradation of proteins like ATXN3 (PubMed:21625540). The J domain is required to reduce PRKN cytoplasmic aggregation (PubMed:20889486). The UIM domains mediate interaction with ubiquitinated chaperone clients and with the proteasome (PubMed:15936278). The UIM domains may have an opposite activity to the J domain, binding ubiquitinated proteins and protecting them from HSP70-mediated proteasomal degradation (PubMed:21625540). The UIM domains are not required to reduce PRKN cytoplasmic aggregation (PubMed:20889486). Ubiquitinated by STUB1; does not lead to proteasomal degradation. The disease is caused by variants affecting the gene represented in this entry.