THEM6 (thioesterase superfamily member 6) is an endoplasmic reticulum (ER) membrane-associated protein that regulates lipid metabolism and cellular stress responses across multiple cancer types. Mechanistically, THEM6 controls intracellular ether lipid levels and triggers ER stress response (UPR) activation, which subsequently modulates sterol biosynthesis and ATF4 signaling 1. In prostate cancer, THEM6 functions as a driver of castration resistance; THEM6 deletion restores androgen-deprivation therapy sensitivity and reduces tumor growth in CRPC models 1. Conversely, in triple-negative breast cancer, THEM6 overexpression enhances carboplatin sensitivity by promoting ferroptosis through stabilization of FDFT1 and inhibition of its K48-linked ubiquitination 2. In breast cancer generally, THEM6 overexpression correlates with poor overall survival and increased tumor cell proliferation, invasion, and reduced apoptosis, while modulating immune infiltration via CCL2-mediated macrophage recruitment 3. In bladder cancer, elevated THEM6 expression associates with immunosuppression in the tumor microenvironment and luminal molecular subtype, while low THEM6 predicts basal subtype responsiveness to immunotherapy 4. These context-dependent roles suggest THEM6 represents a promising therapeutic target, though optimal targeting strategies may vary by cancer type and molecular context.