Proteins are biopolymers generally synthesized from twenty different amino acid monomers. Considering that a typical protein consists of approximately 400 amino acids, there exists an incredibly vast protein sequence space with a wide array of possible combinations. However, functional proteins are found in only a very small fraction of these combinations, with the majority being nonfunctional proteins. In this talk, I will discuss protein misassembly found within nonfunctional protein sequences related to major neurodegenerative diseases and how these protein misassembly systems are linked to comorbidities. Additionally, I will discuss the prevalence of protein misassembly in proteins not associated with diseases. Finally, I will briefly share our recent research efforts to develop computational tools that enable efficient searches for functional proteins with desired properties within the vast protein sequence space.