KLHL2 (kelch like family member 2) functions as a substrate-specific adaptor protein in BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complexes, mediating the ubiquitination and proteasomal degradation of target proteins 1. The protein directly interacts with and promotes degradation of WNK kinases (WNK1, WNK3, WNK4), which are critical regulators of blood pressure through ion transporter control in the kidney 12. KLHL2 also ubiquitinates other substrates including UCK1 (uridine-cytidine kinase 1), with this activity being antagonized by deubiquitinase USP28 3. Additionally, KLHL2 interacts with neuronal pentraxin NPCD, promoting its ubiquitination and aggresome formation, which can lead to neuronal apoptosis when overexpressed 4. In disease contexts, KLHL2 dysfunction contributes to diabetic vascular complications through impaired WNK kinase degradation 5, while its regulation of UCK1 affects sensitivity to chemotherapy in acute myeloid leukemia 3. The protein has also been identified as a neuroticism-associated gene with brain-specific expression patterns 67. Beyond ubiquitin ligase activity, KLHL2 plays roles in actin cytoskeleton reorganization and promotes growth of cell projections in oligodendrocyte precursors.