Ceroid-lipofuscinosis, neuronal 8 transmembrane ER and ERGIC protein (CLN8)

Ceroid-lipofuscinosis, neuronal 8 transmembrane ER and ERGIC protein (CLN8) is a polytopic transmembrane protein predominantly localized to the endoplasmic reticulum (ER) and shuttling between the ER and ER-Golgi intermediate compartment (ERGIC)[1][2][3][4]. CLN8 plays a central role in the trafficking of soluble lysosomal enzymes from the ER to the Golgi apparatus, acting as a cargo receptor essential for proper lysosome biogenesis and function[2][3][4]. It interacts with the protein CLN6 to form the EGRESS complex, which recruits lysosomal proteins and ensures their correct export from the ER[1][3][4]. In addition to its trafficking function, CLN8 is involved in cellular lipid metabolism and may act as a sphingolipid sensor, thereby modulating ceramide-dependent signaling[1]. Mutations in CLN8 cause a neurodegenerative lysosomal storage disorder known as neuronal ceroid lipofuscinosis 8 (NCL8 or Batten disease), commonly presenting as childhood-onset epilepsy and progressive cognitive decline[1][2][3][4]. Loss of CLN8 function leads to impaired delivery of lysosomal enzymes, lysosomal enzyme deficiency, and subsequent neurodegeneration due to defective lysosome biogenesis[1][2][4]. No small-molecule drugs directly targeting CLN8 are currently known.

Other names

Protein CLN8C8orf61FLJ39417TLCD6EPMRceroid-lipofuscinosis neuronal 8transmembrane ER and ERGIC proteinCLN8 transmembrane ER and ERGIC protein