As a physician-scientist, Perlmutter is internationally recognized for his research on alpha-1 antitrypsin deficiency (ATD), a genetic disorder in which accumulations of a misfolded protein can cause severe liver damage. His work has led to advances in the understanding of how cells dispose of misfolded proteins that cause cellular dysfunction as well as the development of a pipeline of ATD drugs that could eliminate the need for liver transplantation in those with the disorder. Since drugs in this pipeline target and enhance autophagy, a cellular degradation pathway which is critical for the functioning of all cells and declines with age, they also represent exciting candidates for prevention of cognitive decline and other degenerative diseases of aging. Through his research, his team has recently discovered a lead candidate drug that targets a natural cellular pathway in a way that may slow, or even prevent, age-dependent degenerative diseases of the liver, heart, and nervous system.