DEFB4B (defensin beta 4B) encodes an antimicrobial peptide belonging to the β-defensin family, primarily expressed in epithelial tissues, particularly keratinocytes 1. The gene functions as an IL-17A-responsive effector involved in innate immune defense mechanisms 2. DEFB4B expression is significantly upregulated in inflammatory skin conditions. In equine supporting limb laminitis, DEFB4B shows 5-200 fold elevation depending on disease severity, expressed predominantly in suprabasal keratinocytes 2. Similarly, in human psoriasis, DEFB4B expression correlates with disease severity and is downregulated following IL-17A blockade therapy 1. The gene is also upregulated in generalized pustular psoriasis, hidradenitis suppurativa, and psoriasis exacerbated by metabolic comorbidities 345. Conversely, smoking and certain genetic variants reduce DEFB4B expression, potentially compromising mucosal immunity 67. Rapid downregulation of DEFB4B occurs with effective topical anti-psoriatic treatment, suggesting therapeutic relevance 8. These findings establish DEFB4B as an IL-17A-regulated antimicrobial peptide serving as both a biomarker and therapeutic target in inflammatory dermatological and immune-mediated conditions.