CLN3, at the crossroads of endocytic trafficking

The CLN3 gene was identified over two decades ago, but the primary function of the CLN3 protein remains unknown. Recessive inheritance of loss of function mutations in CLN3 are responsible for juvenile neuronal ceroid lipofuscinosis (Batten disease, or CLN3 disease), a fatal childhood onset neurodegenerative disease causing vision loss, seizures, progressive dementia, motor function loss and premature death. CLN3 is a multipass transmembrane protein that primarily localizes to endosomes and lysosomes. Defects in endocytosis, autophagy, and lysosomal function are common findings in CLN3-deficiency model systems. However, the molecular mechanisms underlying these defects have not yet been fully elucidated. In this mini-review, we will summarize the current understanding of the CLN3 protein interaction network and discuss how this knowledge is starting to delineate the molecular pathogenesis of CLN3 disease. Accumulating evidence strongly points towards CLN3 playing a role in regulation of the cytoskeleton and cytoskeletal associated proteins to tether cellular membranes, regulation of membrane complexes such as channels/transporters, and modulating the function of small GTPases to effectively mediate vesicular movement and membrane dynamics.

Automated summary

The CLN3 gene was discovered over two decades ago, but the exact function of its protein remains unknown. Loss of function mutations in CLN3 lead to juvenile neuronal ceroid lipofuscinosis, a fatal childhood onset neurodegenerative disease characterized by vision loss, seizures, progressive dementia, and premature death. Evidence suggests that CLN3 may play a role in regulating the cytoskeleton, membrane complexes, and small GTPases to mediate vesicular movement and membrane dynamics.