D-Bifunctional Protein Deficiency
https://www.nature.com/articles/s41467-025-57793-8
Peroxisomes are intracellular organelles that are involved in many key functions, including i) the production of acetyl-CoA, one of the major energy sources in the cell, via HSDB17BA (or D-bifunctional protein), and ii) cilia formation, a sensory organelle at the cell surface which is involved in various major cellular processes. Interestingly, HSDB17BA deficiency and ciliary dysfunction both result in similar clinical symptoms, such as growth retardation and motor dysfunction. The current study used cellular and animal models to investigate the potential link between these two pathologies. They showed, in multiple models, including patient-derived fibroblasts, that the absence of the HSD17B4 geneled to ciliary defects. They further demonstrated that restoring the expression of the HSDB17BA protein and supplementing with acetate both restored acetyl-CoA levels, rescued ciliary function and improved pathological features. These observations highlighted the association between HSDB17BA deficiency and ciliopathy and opened the path for exploring metabolic interventions in these diseases.