Kelch-like family member 17 (KLHL17)

Kelch-like family member 17 (KLHL17), also called Actinfilin, is a **brain-enriched BTB–Kelch protein** primarily expressed in neurons across most brain regions[1]. It contains a BTB domain at the N-terminus for protein dimerization and a Kelch domain at the C-terminus for F-actin binding. KLHL17 is crucial for **actin cytoskeleton regulation** and participates in dendritic spine maturation, localization next to postsynaptic F-actin, and dendritic spine enlargement while maintaining spine density and length. It functions as a substrate adaptor within Cullin3-based E3 ubiquitin ligase complexes, facilitating ubiquitination and degradation of synaptic proteins such as the kainate receptor subunit GluR6, thereby regulating synaptic receptor levels. Dysregulation or loss of KLHL17 in animal models results in abnormal synaptic structure, perturbed neural function, and behavioral phenotypes. Altered expression or methylation status of KLHL17 has also been noted in certain cancers, so it may have disease relevance beyond neurobiology[1][2]. **Key context:** KLHL17 is not a traditional drug target but is structurally and functionally important within the nervous system, with potential implications in neurodevelopmental and oncological disorders. There are no therapeutics or direct clinical targeting strategies currently known for KLHL17.

Other names

Kelch-like protein 17ActinfilinAFKLHL17kelch-like protein 17actinfilinkelch-like 17