CACYBP (calcyclin-binding protein/Siah-1-interacting protein) is a 30 kDa multifunctional protein serving as a molecular adaptor in ubiquitin-mediated proteolysis and calcium-dependent signaling. Primary function: CACYBP participates in beta-catenin degradation within SCF ubiquitin ligase complexes 1 and protects signaling proteins like Myd88 from proteasomal degradation by competing with E3 ligases 2. Mechanism: The protein binds multiple targets including S100 family members, cytoskeletal proteins (tubulin), and kinases (ERK1/2) 3, functioning as a calcium-dependent regulatory hub. In neurons, CACYBP regulates proteostasis through the unfolded protein response pathway, with astrocyte-derived S100A6 inhibiting CACYBP-mediated signaling to modulate neuritogenesis 4. Disease relevance: CACYBP is overexpressed in multiple cancers and promotes proliferation through G1/S transition regulation via Cyclin E/CDK2 upregulation 5. In hepatocellular carcinoma, CACYBP-Myd88 signaling enhances immunosuppressive tumor microenvironment through CX3CL1 transcription, promoting macrophage infiltration 2. Altered CACYBP subcellular localization correlates with Alzheimer's disease pathology 1. Clinical significance: CACYBP inhibition sensitizes anti-PD-1 immunotherapy in HCC and represents a therapeutic target in cancer and neurodegeneration 26.