KLHL35 (kelch like family member 35) is a substrate adaptor protein functioning within the Cul3-RING ubiquitin ligase complex to mediate proteasome-dependent protein degradation [GO Annotations]. While its primary molecular mechanism involves ubiquitin-dependent protein catabolism in the cytoplasm, emerging evidence links KLHL35 dysregulation to multiple diseases. In cancer biology, KLHL35 is significantly overexpressed across 13 tumor types including colorectal cancer, where elevated expression correlates with poor overall survival, progression-free interval, and disease-specific survival 1. In vitro studies confirm KLHL35 promotes cancer cell proliferation, invasion, and migration 1. KLHL35 also exhibits aberrant DNA methylation patterns across diverse pathologies: it is epigenetically silenced in renal cell carcinoma (39% of samples), with RNAi knockdown conferring anchorage-independent growth advantages 2, and hypermethylated in hepatocellular carcinoma where methylation status serves as a diagnostic biomarker 3. Additionally, KLHL35 was identified as a necroptosis-related diagnostic biomarker in Alzheimer's disease 4 and shows differential methylation in abdominal aortic aneurysm pathobiology 5. KLHL35 expression is upregulated during productive HPV16 infection across multiple epithelial tissues 6. Clinically, KLHL35 represents a promising prognostic and diagnostic biomarker candidate across multiple malignancies, though mechanistic studies remain necessary to establish therapeutic targeting feasibility.