Pathogenic variants of the J-domain protein DNAJC12, a co-chaperone of Hsp70, cause parkinsonism, which seems associated with a defective interaction of DNAJC12 with tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine synthesis. Here, we report the characterization of TH:DNAJC12 complex formation and show that DNAJC12 binding stabilizes TH and delays its time-dependent aggregation in an Hsp70-independent manner, while maintaining TH activity and regulatory inhibition by dopamine. Interestingly, although neither TH nor DNAJC12 alone significantly [MDT1] [AM2] activate Hsc70, the complex stimulates [AM3] its ATPase activity. Cryoelectron microscopy reveals two DNAJC12 monomers bound per TH tetramer, each embracing one of the two regulatory domain dimers, leaving all active sites available for substrate and dopamine interaction. Biochemical data confirm the key role of the DNAJC12 last eight residues in TH binding, explaining the molecular disease mechanism of C-terminal truncated DNAJC12 variants.