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Frontotemporal degeneration (FTD) is a heterogeneous spectrum of neurodegenerative disorders characterized by diverse clinical presentations, neuropathological characteristics, and underlying genetic causes. In the last few years, several advances in the knowledge of clinical and biological aspects have been accomplished and three major scenarios have emerged that will represent the core issues in the FTD scene over the next few years. Foremost, the development of cerebrospinal fluid and blood biomarkers as well as neuroimaging techniques will aid the pursuit of new diagnostic and prognostic markers able to identify the ongoing proteinopathy and predict disease progression, which is key in identifying and stratifying patients for enrolment in clinical trials as well as evaluating response to treatment. On the other hand, current research has focused on the first attempts to slow down or revert disease progression, with the identification of disease modulators associated with disease onset and the ongoing development of the first pharmacological treatments for both sporadic and genetic FTD. Future research will certainly improve our knowledge of FTD and possibly open up a new era of disease-modifying therapies for this still-orphan disorder.

Niemann–Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disorder with extensive biological, molecular, and clinical heterogeneity. Recently, numerous studies have tried to shed light on the pathophysiology of the disease, highlighting possible disease pathways common to other neurodegenerative disorders, such as Alzheimer’s disease and frontotemporal dementia, and identifying possible candidate biomarkers for disease staging and response to treatment. Miglustat, which reversibly inhibits glycosphingolipid synthesis, has been licensed in the European Union and elsewhere for the treatment of NPC in both children and adults. A number of ongoing clinical trials might hold promise for the development of new treatments for NPC. The objective of the present work is to review and evaluate recent literature data in order to highlight the latest neuroimaging, neurophysiological, and neuropathological advances for the understanding of NPC pathophysiology. Furthermore, ongoing developments in disease-modifying treatments will be briefly discussed.