Objective:

This literature review examines the roles of the Uncoordinated-13 (UNC13) protein family in the pathogenesis of various human diseases, their implications in neurological and immunological disorders, and their potential therapeutic strategies and directions for future research.

Background:

Recent advancements in molecular research have underscored the significance of the UNC13 protein family in human health, particularly in neurological and immune-related diseases. The UNC13 proteins are evolutionarily conserved and play critical roles in synaptic vesicle priming, exocytosis, and immune cell function. Dysfunction or genetic variations in these proteins have been linked to a range of disorders.

Design/Methods:

A PubMed search was conducted, and relevant articles from the past 20 years were included in the final manuscript. A narrative review was then conducted to investigate the molecular function of the UNC13 protein family and their role in various disease states.

Results:

The UNC13 proteins have been shown to play significant roles in the progression and manifestation of several diseases. UNC13A’s involvement in ALS and FTD is tied to its regulatory role in synaptic plasticity, while UNC13B has been associated with neurodevelopmental and psychiatric disorders, including autism spectrum disorders (ASD) and schizophrenia. UNC13C is implicated in certain cancers, such as oral squamous cell carcinoma and hepatocellular carcinoma, and may serve a protective role in Alzheimer's disease. UNC13D’s key function in immune cell cytotoxicity places it at the center of research into familial hemophagocytic lymphohistiocytosis. The genetic mutations and functional dysregulation of these proteins provide valuable insights into the molecular basis of various disorders.

Conclusions:

The UNC13 protein family is essential to both neurological and immunological processes, and its dysregulation is linked to a broad spectrum of human diseases. Further research is needed to explore these therapeutic possibilities and to fully uncover the molecular mechanisms underpinning the roles of UNC13 proteins in disease.