KLHL17 (Kelch-like family member 17), also known as Actinfilin, is a substrate adaptor protein for Cullin3-based E3 ubiquitin ligase complexes that regulates both neuronal and cancer-relevant cellular processes. As an adaptor component of the BCR(KLHL17) complex, KLHL17 mediates ubiquitination and proteasomal degradation of specific substrates, including the kainate receptor subunit GluR6 1 and, in pancreatic cancer contexts, vimentin and nestin 2. In neurons, KLHL17 functions as an actin-binding protein critical for dendritic spine enlargement through F-actin remodeling 3. KLHL17 regulates glutamate receptor expression via dual mechanisms: it promotes NSF-dependent AMPA receptor surface trafficking while mediating activity-dependent degradation of kainate receptors 4. Functionally, KLHL17 deficiency impairs dendritic spine enlargement, synaptic transmission, and behavioral functions including social interaction 3. Clinically, KLHL17 variants associate with infantile spasms and autism spectrum disorders 35, suggesting roles in synaptic development. In cancer, KLHL17 expression inversely correlates with pancreatic cancer risk 2 and overexpression promotes non-small cell lung cancer proliferation via Ras/MAPK pathway activation 6. KLHL17 has been identified as a tumor antigen candidate for prostate cancer mRNA vaccines 7.