Endoplasmic reticulum junction formation protein lunapark

Lunapark (LNPK) is an endoplasmic reticulum (ER)-shaping membrane protein that stabilizes nascent three-way ER tubular junctions and determines overall ER network morphology (UniProt: Q9C0E8). The protein functions as a curvature-stabilizing factor within the ER junction architecture and plays a role in central nervous system development. It is a 428-amino-acid protein encoded by the LNPK gene in humans.

LNPK is associated with neurodevelopmental pathology, specifically the autosomal recessive disorder neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum (NEDEHCC, MIM 618090), characterized by intellectual disability, seizures, and corpus callosum hypoplasia (UniProt: Q9C0E8).

In Alzheimer's disease, LNPK is downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics). Quantitative proteomics analysis across subcellular fractions detected a mean log2 fold-change of −0.32, indicating reduced expression in the AD brain. This downregulation may reflect impaired ER integrity or altered neuronal morphology in the disease state.