Clathrin-mediated endocytosis (CME) is a fundamental process in which cargo molecules are internalized from the cell surface, packaged into vesicles and trafficked within the cell. In keeping with cargo diversity, CME has different physiological functions, from molecule uptake, receptor internalization, signal transduction to synaptic vesicle recycling. Clathrin is also essential in intracellular processes of several endomembrane systems which consists of an array of organelles including the endoplasmic reticulum (ER), ER-Golgi intermediate compartment (ERGIC), trans Golgi Network (TGN), early and late endosomes, lysosomes, endocytic recycling compartment and different domains of plasma membrane.

Several proteins and regulatory elements are involved in the pathway, polymerizing the clathrin lattice, promoting the formation of clathrin-coated vesicles, triggering vesicle scission, functioning as scaffolding proteins, removing the clathrin coat or sorting and transporting membrane proteins within the cell.

CME and the involved proteins play important functions in most cells but are particularly essential for proper neural functions. It is therefore not surprising that dysfunctions or dysregulations of the pathway are common hallmarks of several neurological diseases.

Furthermore, several genes, coding for proteins involved in processes that are closely linked to CME and related intracellular trafficking, have been described as associated, candidate or susceptibility genes in neurological and psychiatric disorders. As examples, variants in PICALM or in BIN1, key components of the CME machinery, have been described as risk factors for late-onset Alzheimer’s disease. Mutations in genes like LRRK2, DNAJC13, DNAJC6, GAK, SYNJ1, implicated in the clathrin-mediated synaptic vesicle cycle, are involved in familial and sporadic Parkinson’s disease. Genetic association studies have demonstrated a link between schizophrenia and mutations in genes encoding for proteins that directly interact with or are functionally linked to clathrin-mediated pathways, such as STON2, CLINT1, DTNBP1, DISC1. Adaptinopathies are a new class of neurocutaneous and neurometabolic disorder affecting intracellular trafficking, mediated by clathrin-coated vesicles and their assembly requires adaptor protein complexes. Some of these genetic disorders also display a neurological phenotype, like MEDNIK syndrome, caused by AP1S1 mutations. Mutations in DNM2, a GTPase involved in CME, have been implicated in hereditary disorders of the peripheral nervous system, like Charcot Marie Tooth disease. Mutations in the ALS2 gene, in a recessive form of juvenile amyotrophic lateral sclerosis, deregulate early endosome maturation and cargo sorting.

This Special Issue invites researchers and clinicians to submit both original research and review manuscripts, with the aim of providing a more comprehensive overview of the role of CME and related intracellular trafficking in neurological and psychiatric diseases.

Potential topics include but are not limited to the following:

• Animal and cellular models, depicting the role of CME and related intracellular trafficking in neurological and psychiatric disorders
• Basic science studies on human neuropathologies, in which CME and related intracellular trafficking are involved
• Genetic studies on CME-related neurological and psychiatric disorders
• Therapeutic interventions in CME-related neuropathologies