{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DNAJC12 is a member of the HSP40 (DnaJ) family that functions as a co‐chaperone, acting in concert with HSP70 partners to regulate the folding, assembly, and stability of client proteins. In particular, DNAJC12 facilitates the proper folding and maintenance of key enzymes such as phenylalanine hydroxylase and the other aromatic amino acid hydroxylases, a function essential for normal neurotransmitter synthesis and metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Disruption of this activity due to biallelic mutations in DNAJC12 has been linked to hyperphenylalaninemia and an array of neurological disturbances including movement disorders, intellectual disability, and dopa‐responsive non‐progressive parkinsonism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " These observations are further supported by studies in which patient‐derived cells and induced pluripotent stem cell models have been used to elucidate the underlying pathomechanisms of DNAJC12 deficiency."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its established role in maintaining proteostasis in neurotransmitter metabolism, aberrant DNAJC12 expression has also been implicated in oncogenesis. In certain tumor types such as lung and gastric cancers, increased DNAJC12 expression is associated with enhanced cell proliferation, migration, and invasion, possibly through modulation of the β‑catenin signaling pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, in breast carcinoma, DNAJC12 appears to be under transcriptional control by estrogen receptor signaling and positively correlates with ERBB4 expression, suggesting a role in hormone‐mediated transcriptional networks in cancer cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, the detection of DNAJC12 mutations in newborn screening programs for hyperphenylalaninemia emphasizes its clinical importance in inherited metabolic disorders and suggests that early therapeutic intervention—combining dietary control with tetrahydrobiopterin and neurotransmitter precursor supplementation—can mitigate neurodevelopmental impairment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jin Choi, Sonia Djebbar, Andréa Fournier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The co-chaperone DNAJC12 binds to Hsc70 and is upregulated by endoplasmic reticulum stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Stress Chaperones (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12192-013-0471-6"}], "href": "https://doi.org/10.1007/s12192-013-0471-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24122553"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24122553"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kunwar Jung-Kc, Nastassja Himmelreich, Karina S Prestegård, et al. 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