SQLE (squalene epoxidase) is a rate-limiting enzyme in cholesterol biosynthesis that catalyzes the oxidation of squalene to epoxysqualene 1. Located in the endoplasmic reticulum, SQLE plays crucial roles beyond basic sterol synthesis. In cancer, SQLE promotes tumor growth through multiple mechanisms: it maintains lipid raft stability and activates oncogenic Src/PI3K/Akt signaling pathways 2, while its inhibition leads to squalene accumulation-induced ER stress and apoptosis 2. SQLE creates immunosuppressive tumor microenvironments by generating cholesterol that impairs CD8+ T cell function and promotes myeloid-derived suppressor cells 3. In hepatocellular carcinoma, SQLE-driven cholesterol accumulation produces oxidized LDL that induces protumorigenic TREM2+ tumor-associated macrophages 4. The enzyme also contributes to metabolic reprogramming in brain tumors, where NR4A2-mediated SQLE activation dysregulates cholesterol homeostasis in microglia 5. Clinically, SQLE represents a promising therapeutic target, as its inhibition with drugs like terbinafine can restore anti-PD-1 immunotherapy efficacy 3 and suppress pancreatic cancer growth 2. Additionally, SQLE mutations in dermatophytes confer resistance to antifungal therapy 6.