The ankyrin repeat is a highly conserved 33-residue motif that forms the basis for modular protein interactions. This motif is found in numerous proteins involved in diverse cellular functions, including cell signaling, cytoskeleton integrity, transcription, and cell cycle regulation. Recent studies have elucidated the structural basis of ankyrin repeat-mediated protein interactions, revealing that these domains typically undergo a two-state folding transition. The ankyrin repeat has a well-defined structure consisting of two antiparallel α-helices followed by a β-hairpin or long loop, forming an L-shaped domain. The stability and folding pathways of ankyrin repeat proteins have been investigated, showing that they generally follow a two-state folding model. Additionally, the ankyrin repeat has been used as a template for consensus-based protein design, leading to the creation of stable and functional protein frameworks. Defects in ankyrin repeat proteins have been linked to various human diseases, such as cancer and developmental disorders, highlighting the importance of understanding their structure and function.The ankyrin repeat is a highly conserved 33-residue motif that forms the basis for modular protein interactions. This motif is found in numerous proteins involved in diverse cellular functions, including cell signaling, cytoskeleton integrity, transcription, and cell cycle regulation. Recent studies have elucidated the structural basis of ankyrin repeat-mediated protein interactions, revealing that these domains typically undergo a two-state folding transition. The ankyrin repeat has a well-defined structure consisting of two antiparallel α-helices followed by a β-hairpin or long loop, forming an L-shaped domain. The stability and folding pathways of ankyrin repeat proteins have been investigated, showing that they generally follow a two-state folding model. Additionally, the ankyrin repeat has been used as a template for consensus-based protein design, leading to the creation of stable and functional protein frameworks. Defects in ankyrin repeat proteins have been linked to various human diseases, such as cancer and developmental disorders, highlighting the importance of understanding their structure and function.