ALDH18A1

Overview

ALDH18A1 is a human gene that encodes delta-1-pyrroline-5-carboxylate synthase (P5CS), an enzyme involved in amino acid and proline biosynthesis. In biomedical literature, ALDH18A1 is recognized as a metabolic gene with relevance to cellular redox balance and broader metabolic regulation. Because it participates in core biosynthetic pathways, changes in its activity or expression can be associated with altered metabolic states in disease contexts.

Beyond its canonical metabolic role, ALDH18A1 has recently appeared in studies exploring disease-associated metabolic remodeling and signaling interactions. In these settings, it has been considered as a potential therapeutic target rather than only as a metabolic enzyme, reflecting growing interest in how metabolic enzymes may contribute to disease-specific pathway dysregulation.

Focus of Latest Publications

Recent research has highlighted ALDH18A1 in two distinct disease-oriented contexts.

In a study of Alzheimer's disease subtypes, ALDH18A1 was identified through a human genome-scale metabolic network approach as a subtype-specific candidate drug target. The study focused on aberrant metabolic patterns in Alzheimer's disease, including perturbed metabolic pathways and candidate metabolite biomarkers. Within this framework, the authors reported that upregulated secretion of pregnenolone and N-acetylneuraminate emerged as candidate metabolite biomarkers, while ALDH18A1 and SLC6A12 were predicted as therapeutic targets for subtype-specific intervention. The publication states that these predictions were supported by available literature, and it specifically mentions Alzheimer's disease in the broader research context. This positions ALDH18A1 as part of a systems-level metabolic signature relevant to disease stratification and target prioritization.

In a separate study focused on airway epithelial cells from aged mouse lungs, ALDH18A1 was described as downregulated in parallel with NRF2. The title and context indicate that ALDH18A1 was investigated in relation to phosphorylation of Cullin3 and disruption of KEAP1-mediated NRF2 degradation, linking it to the NRF2 antioxidant pathway. The publication also references Nrf2-associated antioxidant genes, suggesting that ALDH18A1 was considered within a broader antioxidant and stress-response network. The provided context does not establish ALDH18A1 as a direct kinase in the conventional sense, but it does indicate that the protein was examined in a signaling framework involving Cullin3, KEAP1, and NRF2 regulation. The mention of the T299I variant in the extracted study context suggests that a specific ALDH18A1-related alteration was part of the experimental or analytical setup, although the supplied text does not provide further detail on its functional interpretation.

Together, these studies present ALDH18A1 as a gene of interest in both metabolic disease modeling and stress-response signaling, with potential relevance to Alzheimer's disease subtype biology and age-associated pulmonary changes.

Key Publications

• Jun Unraveling Aberrant Metabolic Patterns in Alzheimer's Disease Subtypes: From Perturbed Metabolic Pathways to Candidate Drug Targets. (Molecular neurobiology, 2026, PMID 42313214): "Moreover, upregulated secretion of pregnenolone and N-acetylneuraminate and therapeutic targeting of ALDH18A1 and SLC6A12 were among the subtype-specific candidate metabolite biomarkers and drug targets, respectively, predicted by our metabolic modeling approach, with available literature support."
• Jun Phosphorylation of Cullin3 by the pseudokinase ALDH18A1 disrupts KEAP1-mediated NRF2 degradation. (Biochemical and biophysical research communications, 2026, PMID 41996736): "Here we show that ALDH18A1 (P5CS) is downregulated in parallel with NRF2 in the airway epithelial cells of aged mouse lungs."