CLN5 deficiency impairs glucose uptake and uncovers PHGDH as a potential biomarker in Batten disease.

ABSTRACT: CLN5 disease, a form of juvenile dementia within the neuronal ceroid lipofuscinosis (NCL), is associated with mutations in the CLN5 gene encoding the lysosomal bis(monoacylglycero)phosphate (BMP) synthase, essential for BMP production and lysosomal function. Limited knowledge of cellular mechanisms and unclear drug targets hinder translating this to children's treatment, which remains symptomatic. We developed and characterized a new cln5 knock-out zebrafish model that replicates key features and molecular signatures of the human disease. Loss of Cln5 function in vivo altered axonal growth of retinal ON-bipolar cells and disrupted calcium homeostasis in the cerebellum, revealing new disease features. Additionally, multi-omic analyses at different developmental stages revealed an impaired g

SUBMITTER: Marchese M 

PROVIDER: S-EPMC12436169 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature