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The mammalian central nervous system (CNS) is composed of hundreds of distinct cell types. In spite of extensive knowledge regarding the molecular basis of some aspects of differential cell type form and function, it is not yet well understood how molecular differences predispose particular neurons to differential vulnerability in the most common neurodegenerative diseases. In this seminar, I will discuss our recent efforts to characterize specific classes of CNS neurons at the molecular level, and to utilize this information to understand their function and dysfunction in neurodegenerative diseases such as Huntington’s disease.