The chemical and structural properties of protein determine their interactions, and thus their functions, in a wide variety of biochemical processes. Since Ruggeri et al. pioneering work on the aggregation pathways of the Josephin domain of ataxin-3, responsible for type-3 spinocerebellar ataxia, an inheritable protein-misfolding disease, AFM-IR was used to characterize molecular conformations in a wide spectrum of applications in protein and life sciences. This approach has delivered new mechanistic insights into the behaviour of disease-related proteins and peptides, such as Aβ42, huntingtin and FUS, which are involved in the onset of Alzheimers, Huntingtons and Amyotrophic lateral sclerosis (ALS). Similarly AFM-IR has been applied to study studying protein based functional biomaterials.