{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Aspartoacylase‐3 (ACY3) is an enzyme that catalyzes deacetylation reactions and appears to play diverse roles in human physiology and disease. Several studies indicate that ACY3 can affect drug responses, cancer progression, infectious pathogenesis, and neurodegeneration. For example, genetic variation in the ACY3 locus has been associated with differential responses to beta‐blockers used for treating hypertension, suggesting that ACY3 may contribute to interindividual differences in antihypertensive drug efficacy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In neuroblastoma, ACY3 exhibits a nuclear localization pattern and higher expression levels correlate with poor clinical prognosis, implicating the enzyme in tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, ACY3 has been identified as a binding partner of the hepatitis C virus core protein, which suggests that its activity may be linked to viral pathogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Evolutionary analyses further propose that ACY3, in conjunction with related enzymes such as ASPA, may have originated from ancient bacteria‐to‐animal horizontal gene transfer events."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Proteomic investigations in diabetic kidney disease have revealed upregulation of ACY3 in affected glomeruli, hinting at a potential role in disease‐related metabolic disturbances."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In studies of neurodegenerative disorders, increased ACY3 expression has been observed in the context of polyglutamine diseases—particularly within oligodendrocytes in spinocerebellar ataxia type 3—suggesting that altered ACY3 activity may contribute to early white matter dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Additionally, co‐expression analyses in cutaneous squamous cell carcinoma have identified ACY3 among a group of mRNAs linked with long noncoding RNAs implicated in endoplasmic reticulum stress, apoptosis, and autophagy, which further supports a function of ACY3 in cancer progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, ACY3 is a multifunctional enzyme whose deacetylase activity may influence metabolic regulation, modify drug response, and participate in pathways underlying oncogenesis, neurodegeneration, and viral infection. Collectively, these findings suggest that ACY3 is an important mediator of cellular homeostasis and its dysregulation could contribute to diverse pathological conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "3", "end_ref": "8"}, {"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Timo P Hiltunen, Kati M Donner, Antti-Pekka Sarin, et al. 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