CARD18 (caspase recruitment domain family member 18) is a caspase-1 inhibitor that suppresses inflammatory responses by binding to caspase-1 and preventing its association with RIP2, thereby downregulating IL-1β production 1. CARD18 contains a caspase recruitment domain (CARD) that enables homotypic interactions to cap caspase-1 filaments, exerting potent inhibition of inflammasome polymerization with low-nanomolar affinity 2. CARD18 is specifically expressed in the granular layer of normal epidermis at over 100-fold higher levels than other tissues and is upregulated during keratinocyte terminal differentiation 1. Expression increases following UV irradiation but is markedly downregulated or absent in lesional epidermis of lichen planus patients, suggesting a role in epidermal inflammatory responses 1. Clinically, CARD18 dysregulation is associated with multiple pathologies. In periodontal disease, CARD18 downregulation correlates with active disease and elevated NLRP3/IL-1β activity 3. In esophageal squamous cell carcinoma, CARD18 expression predicts prognosis and relates to lymph node metastasis and TNM stage 4. Notably, spironolactone therapy in heart failure with preserved ejection fraction substantially upregulates CARD18 (+66.5%), suggesting potential antiapoptotic effects 5. In actinic keratosis progression to carcinoma, CARD18 expression in stromal lymphocytes distinguishes regression from progression groups 6.