The ankyrin repeat is a common amino acid motif in proteins, involved in various cellular functions and linked to several human diseases. Recent studies have explored its structural and functional properties, revealing that ankyrin repeats form a two-state folding transition despite their modular structure. These repeats are used as a template for consensus-based protein design, enabling the creation of potential universal scaffolds for molecular recognition. Ankyrin repeats are found in many proteins, including those involved in cell signaling, cytoskeleton integrity, and transcription. They typically mediate specific protein-protein interactions without recognizing specific amino acid sequences. Structural studies show that ankyrin repeats form an L-shaped domain with a curved shape, consisting of α-helices and β-hairpins. The stability of ankyrin repeat domains is influenced by hydrophobic interactions and hydrogen bonding. The consensus sequence of ankyrin repeats contains conserved residues that define the repeat's structure. Analysis of ankyrin repeat sequences has shown that the number of repeats per protein varies, with most containing six or fewer repeats. The ankyrin repeat domain of Notch, a signaling protein, contains seven repeats. Ankyrin repeats are also found in various disease-related proteins, such as p16, p18, and p19, which are involved in cell cycle regulation. Mutations in ankyrin repeat proteins can lead to functional defects, affecting their ability to mediate protein-protein interactions. Consensus-based design studies have successfully created stable ankyrin repeat proteins, demonstrating the potential of this motif for protein engineering. Overall, ankyrin repeats play a crucial role in protein-protein interactions and are important for understanding cellular processes and designing therapeutic strategies.The ankyrin repeat is a common amino acid motif in proteins, involved in various cellular functions and linked to several human diseases. Recent studies have explored its structural and functional properties, revealing that ankyrin repeats form a two-state folding transition despite their modular structure. These repeats are used as a template for consensus-based protein design, enabling the creation of potential universal scaffolds for molecular recognition. Ankyrin repeats are found in many proteins, including those involved in cell signaling, cytoskeleton integrity, and transcription. They typically mediate specific protein-protein interactions without recognizing specific amino acid sequences. Structural studies show that ankyrin repeats form an L-shaped domain with a curved shape, consisting of α-helices and β-hairpins. The stability of ankyrin repeat domains is influenced by hydrophobic interactions and hydrogen bonding. The consensus sequence of ankyrin repeats contains conserved residues that define the repeat's structure. Analysis of ankyrin repeat sequences has shown that the number of repeats per protein varies, with most containing six or fewer repeats. The ankyrin repeat domain of Notch, a signaling protein, contains seven repeats. Ankyrin repeats are also found in various disease-related proteins, such as p16, p18, and p19, which are involved in cell cycle regulation. Mutations in ankyrin repeat proteins can lead to functional defects, affecting their ability to mediate protein-protein interactions. Consensus-based design studies have successfully created stable ankyrin repeat proteins, demonstrating the potential of this motif for protein engineering. Overall, ankyrin repeats play a crucial role in protein-protein interactions and are important for understanding cellular processes and designing therapeutic strategies.