MYLIP (myosin regulatory light chain interacting protein) is an E3 ubiquitin ligase with primary functions in cholesterol homeostasis and hypoxia signaling regulation. As a sterol-dependent inhibitor of cellular cholesterol uptake, MYLIP mediates ubiquitination and proteasomal degradation of the LDL receptor (LDLR) 1, with LXR ligands inducing MYLIP expression to suppress LDL uptake 2. MYLIP also targets lipoprotein(a) uptake by negatively regulating LDLR abundance 3. Beyond lipid metabolism, MYLIP catalyzes K27-linked polyubiquitination of HIF-1α and HIF-2α at specific lysine residues, promoting their proteasomal degradation and attenuating hypoxia tolerance 4. This function contrasts with its cholesterol-regulatory role, suggesting pleiotropic cellular functions. Disease relevance includes dysregulation in cervical cancer, where MYLIP overexpression promotes cell growth and metastasis when miR-802 is downregulated 5, and breast cancer, where MYLIP expression is suppressed through the TUSC8/miR-190b-5p axis to inhibit metastasis 6. Clinically, MYLIP polymorphisms (rs3757354) associate with early-onset preeclampsia risk in Chinese women 7. These findings establish MYLIP as a multi-functional regulator linking lipid metabolism, hypoxia signaling, and cancer progression.