CYSLTR2 encodes cysteinyl leukotriene receptor 2, a G-protein-coupled receptor that responds to cysteinyl leukotrienes (LTC4, LTD4, LTE4) with LTC4 showing the highest affinity 1. The receptor activates phosphatidylinositol-calcium second messenger systems and mediates immune and inflammatory responses [UniProt]. Beyond classical leukotriene signaling, CYSLTR2 functions as an endogenous receptor for long-chain ceramides (C16:0 and C20:0), which bind to a channel-like pocket on the receptor and activate Gq-mediated inflammasome signaling in endothelial cells and macrophages 2. This ceramide-sensing function contributes to atherosclerosis progression and chr13 kidney disease-associated vascular disease 2. In allergic diseases, CYSLTR2 variants influence individual response to leukotriene-modifying asthma medications 3. CYSLTR2 is highly expressed in dorsal root ganglia neurons and mediates LTC4-induced itch in allergic skin inflammation and atopic dermatitis models, providing a therapeutic target for inflammatory itch 1. Clinically, CYSLTR2 mutations represent rare but significant oncogenic drivers in melanoma. Activating CYSLTR2 mutations (particularly p.L129Q) initiate uveal melanoma development through G-protein signaling activation, constituting an alternative to more common GNAQ/GNA11 mutations 45. CYSLTR2 mutations also occur in malignant blue melanoma, a cutaneous variant with poor prognosis 6. These findings establish CYSLTR2 as a dual-function receptor linking inflammatory signaling to oncogenic transformation.