Kelch-like protein 24 (KLHL24)

Kelch-like protein 24 (KLHL24) is a member of the BTB-Kelch family of proteins that functions as a substrate receptor in the BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex[3][4]. In this role, it mediates ubiquitination and subsequent proteasomal degradation of specific substrates, especially intermediate filament proteins such as keratin 14 in keratinocytes, maintaining the balance of cytoskeletal stability and turnover required for skin integrity[2][3]. KLHL24 also regulates desmin and vimentin intermediate filaments, which are important for cardiac muscle and fibroblast function, respectively[1][2]. Mutations in KLHL24 that alter protein stability or function cause severe genetic diseases such as epidermolysis bullosa simplex and both dilated and hypertrophic cardiomyopathy, likely due to dysregulated turnover of its substrate filaments in the skin and heart[1][2][4]. In the nervous system, KLHL24 modulates the function of kainate-type glutamate receptors, but its primary clinical significance is in skin and cardiac disease[2][4]. Various alternative names and gene designations have been used for KLHL24, related to its functional discovery in different systems. Therapeutic strategies would theoretically target pathological ubiquitination but currently, no drugs act directly on KLHL24.

Other names

Kelch-like family member 24KLHL24DRE1KRIP6FLJ20059Kainate receptor-interacting protein for GluR6Protein DRE1CMH29EBS6EBSSHkelch-like protein 24kainate receptor interacting protein for GluR6kelch-like 24