Ceroid-lipofuscinosis neuronal protein 5 (CLN5) (CLN5)

Ceroid-lipofuscinosis neuronal protein 5 (CLN5) is a soluble lysosomal glycoprotein encoded by the CLN5 gene [UniProt, Wikipedia]. It functions as a bis(monoacylglycero)phosphate (BMP) synthase, an enzyme essential for the synthesis of BMP, which is critical for maintaining lysosomal membrane integrity and regulating cholesterol homeostasis [NIH, GeneCards]. Mutations in the CLN5 gene lead to CLN5 disease, a rare and fatal neurodegenerative disorder classified as a variant late-infantile form of Batten disease [MedlinePlus, University of Rochester]. The disease is characterized by the accumulation of autofluorescent storage material (lipofuscin) in neurons, resulting in progressive motor dysfunction, vision loss, seizures, and cognitive decline [NIH, Batten Disease News]. Therapeutic efforts are primarily focused on gene replacement therapy, such as NGN-101, which utilizes adeno-associated virus (AAV) vectors to deliver a functional CLN5 gene to the central nervous system [Batten Disease News, University of Rochester]. While these therapies aim to halt disease progression, challenges include ensuring widespread protein distribution and addressing ocular symptoms that may not be fully resolved by intracranial delivery [Frontiers in Genetics, NIH].

Other names

CLN5 Lysosomal BMP SynthaseCLN5 Intracellular Trafficking ProteinLysosomal Bis(Monoacylglycero)Phosphate SynthaseCeroid-Lipofuscinosis Neuronal Protein 5Palmitoyl Protein Thioesterase CLN5S-Depalmitoylase CLN5BMPS

Gene replacement therapy using an adeno-associated virus (AAV) vector to deliver a functional copy of the CLN5 gene to restore protein expression and lysosomal function [Batten Disease News, University of Rochester].