ELOVL3 is a very long-chain fatty acid elongase that catalyzes the first and rate-limiting step of fatty acid elongation, adding 2 carbons to long- and very long-chain fatty acids (VLCFAs) per cycle 1. The enzyme is localized to the endoplasmic reticulum and exhibits higher activity toward saturated C18 acyl-CoAs, serving as a condensing enzyme for both saturated and unsaturated substrates. ELOVL3 plays critical roles in skin barrier function and lipid homeostasis. In atopic dermatitis, dupilumab treatment significantly increases ELOVL3 expression alongside epidermal differentiation and barrier gene upregulation, correlating with clinical improvement 2. Conversely, Staphylococcus aureus colonization suppresses ELOVL3 expression through IL-1β, TNF-α, IL-6, and IL-33, leading to aberrant lipid composition and increased transepidermal water loss 3. Similarly, seborrheic dermatitis shows ELOVL3 downregulation alongside barrier dysfunction 4. Th1/Th17 cytokines specifically downregulate ELOVL3 in psoriasis-like conditions 5. Beyond skin, ELOVL3 expression is circadianly regulated in liver by RevErbalpha and SREBP1, integrating clock and nutritional signals 6. In meibomian glands, ELOVL3 is essential for producing C21:0-C29:0 fatty acids; knockout mice display ocular surface pathology 1. Clinically, dysregulated ELOVL3 is implicated in prostate cancer metastasis through BRG1-mediated transcriptional activation 7.