Kelch-like protein 42

Kelch-like protein 42 (KLHL42) is a substrate adapter of the BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that regulates mitotic progression and cytokinesis (UniProt: Q9P2K6). The complex mediates ubiquitination and degradation of KATNA1, thereby modulating microtubule dynamics during mitosis.

KLHL42 is a 505-amino-acid protein with a molecular mass of approximately 57 kDa. No disease associations are documented in UniProt for this protein, though it plays a critical role in cell-cycle regulation through its involvement in ubiquitin-mediated proteolysis.

In Alzheimer's disease, KLHL42 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change −0.39; Chaparral AD proteomics). This downregulation was detected across subcellular fractions in a TMT-labeled quantitative proteomics study. The reduced expression of this mitotic regulator may reflect broader cellular cycle dysregulation observed in AD pathology.