KLHL5 (kelch like family member 5) is a BTB and kelch repeat-containing protein that functions as a substrate adaptor for the Cullin3-RING E3 ubiquitin ligase complex 1. It mediates proteasomal degradation of target proteins through lysine ubiquitination, including sphingosine kinase 1 at lysine 183 2. KLHL5 is abundantly expressed in ovary, adrenal gland, and thyroid tissues 1. In cancer pathophysiology, KLHL5 promotes malignant progression across multiple cancer types. In colorectal cancer (CRC), KLHL5 is highly expressed relative to normal mucosa, with expression correlating with advanced stage, depth of invasion, lymphovascular invasion, and lymph node metastasis 3. Mechanistically, KLHL5 enhances CRC cell survival by promoting cell cycle progression through upregulation of CDT1, CDC6, and cyclins A and B, while simultaneously suppressing apoptosis via regulation of anti- and pro-apoptotic factors 4. In gastric cancer, the miR-181-5p/KLHL5 axis promotes proliferation and migration by activating METTL3-mediated m6A RNA modification 5. KLHL5 is also associated with neuropathic pain pathogenesis 6 and appears relevant to Alzheimer's disease neuroinflammation 7. Clinically, KLHL5 serves as a potential prognostic biomarker and therapeutic target for CRC and other cancers due to its role in tumor progression and poor survival outcomes.