Human cytomegalovirus (HCMV) persistently infects 60-90% of people worldwide, causing significant morbidity and mortality in the immunocompromised and congenital infection in 1/100 pregnancies. An increased understanding of HCMV pathogenesis will result from characterisation of critical viral regulators of cellular biology. Using a multiplexed proteomic screen, we previously identified 133 host proteins that are rapidly degraded during early HCMV infection, many of which are known or novel components of innate and adaptive host immune responses, controllers of cell death pathways and regulators of host metabolism. Among these, 3β-hydroxysteroid-Δ24 reductase (DHCR24), a key terminal regulator of cholesterol biosynthesis, was degraded with high confidence.  Recent studies have shown that DHCR24 also regulates host immunity by impairing K27-linked ubiquitination of MAVS and STING. Here, we show that the HCMV US14 protein leads to proteasome-dependent degradation of DHCR24 in human fibroblasts and investigate the mechanisms of this degradation. I will present findings on how DHCR24 and US14 interact, and the consequence of reduced DHCR24 activity for both the host cell, host immunity and viral replication. This work provides new insights into a previously unrecognised strategy of viral immune modulation, and may inform future approaches to ameliorating HCMV pathogenesis.